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  • Needle-free injectors for mass administration of fractional dose inactivated poliovirus vaccine in Karachi, Pakistan: A survey of caregiver and vaccinator acceptability
    Vaccine (IF 3.269) Pub Date : 2020-01-23
    Catherine Daly; Natalia A. Molodecky; Meghana Sreevatsava; Asalif D. Belayneh; Shoukat A. Chandio; Jeff Partridge; Ahmed Shaikh; Mumtaz Laghari; John Agbor; Rana M. Safdar; Umar Farooq Bullo; Safi M. Malik; Abdirahman Mahamud

    The first large-scale vaccination campaign using needle-free jet injectors to administer fractional doses of inactivated poliovirus vaccine (fIPV) was conducted in Karachi, Pakistan, in February 2019. Data on acceptability of jet injectors were collected from 610 vaccinators and 4898 caregivers during the first four days of the campaign. Of those with prior needle and syringe experience, both vaccinators and caregivers expressed a strong preference for jet injectors (578/592 [97.6%] and 4792/4813 [99.6%], respectively), citing ease of use, appearance, and child’s response to vaccination. Among caregivers, 4638 (94.7%) stated they would be more likely to bring their child for vaccination in a future campaign that used jet injectors. Mean vaccine coverage among towns administering fIPV was 98.7% – an increase by 18.4% over the preceding campaign involving full-dose IPV. Our findings demonstrate the strong acceptability of fIPV jet injectors and highlight the potential value of this method in future mass campaigns.

    更新日期:2020-01-23
  • Design and production of dengue virus chimeric proteins useful for developing tetravalent vaccines
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Izabella Cristina Andrade Batista; Bárbara Resende Quinan; Érica Alessandra Rocha Alves; Soraya Torres Gaze Jangola; Eneida Santos Oliveira; Stella Garcia Colombarolli; Jorge Gomes Goulart Ferreira; Eliseu Soares de Oliveira Rocha; Erna Geessien Kroon; Rafael Ramiro de Assis; Jaquelline Germano de Oliveira; Jacqueline Araújo Fiuza; Carlos Eduardo Calzavara-Silva

    Dengue virus (DENV) is a Flavivirus estimated to cause 390 million infections/year. Currently, there is no anti-viral specific treatment for dengue, and efficient DENV vector control is still unfeasible. Here, we designed and produced chimeric proteins containing potential immunogenic epitopes from the four DENV serotypes in an attempt to further compose safer, balanced tetravalent dengue vaccines. For this, South American DENV isolate sequences were downloaded from the NCBI/Virus Variation/Dengue virus databases and intraserotype-aligned to generate four consensuses. Four homologous DENV sequences were retrieved using BLAST and then interserotype-aligned. In parallel, sequences were subjected to linear B epitope prediction analysis. Regions of the envelope and NS1 proteins that are highly homologous among the four DENV serotypes, non-conserved antigenic regions and the most antigenic epitopes found in the C, prM, E and NS1 DENV proteins were used to construct 11 chimeric peptides. Genes encoding the chimeric proteins were commercially synthesized, and proteins were expressed, purified by affinity chromatography and further subjected to ELISA assays using sera from individuals infected with DENVs 1, 2, 3 or 4. As a proof-of-concept, the chimeric EnvEpII protein was selected to immunize BALB/c and C57BL/6 mice strains. The immunization with EnvEpII protein associated with aluminum induced an increased number of T CD4+ and CD8+ cells, high production of IgG1 and IgG2 antibodies, and increased levels of IL-2 and IL-17 cytokines, in both mouse strains. Because the EnvEpII protein associated with aluminum induced an efficient cellular response by stimulating the production of IL-2, IL-4, IL-17 and induced a robust humoral response in mice, we conclude that it resembles an efficient specific response against DENV infection. Although further experiments are required, our results indicate that epitope selection by bioinformatic tools is efficient to create recombinant proteins that can be used as candidates for the development of vaccines against infectious diseases.

    更新日期:2020-01-23
  • Study of integrated protective immunity induced in rhesus macaques by the intradermal administration of a bivalent EV71-CA16 inactivated vaccine
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Shengtao Fan; Yun Liao; Guorun Jiang; Li Jiang; Lichun Wang; Xingli Xu; Min Feng; Erxia Yang; Ying Zhang; Wei Cui; Qihan Li

    Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are recognized as the major pathogens responsible for human hand-foot-mouth disease. To develop a bivalent EV71-CA16 vaccine, rhesus macaques immunized with two doses of this vaccine via the intradermal route were challenged with EV71 or CA16, and their clinical symptoms, viral shedding, neutralizing antibodies, IFN-γ-specific ELISpots, and tissue viral load were examined longitudinally. Specific immunity against EV71 and CA16 was observed in the macaques, which exhibited controlled proliferation of the EV71 and CA16 viruses and upregulated expression of immune-related genes compared with the controls. Furthermore, broad protection against EV71 and CA16 challenge without immunopathological effects was observed in all the immunized macaques. These studies suggest that the bivalent EV71-CA16 inactivated vaccine was effective against wild-type EV71 or CA16 viral challenge in rhesus macaques.

    更新日期:2020-01-23
  • Immunogenicity and safety profile of a primary dose of bivalent oral polio vaccine given simultaneously with DTwP-Hb-Hib and inactivated poliovirus vaccine at the 4th visit in Indonesian infants
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Eddy Fadlyana; Meita Dhamayanti; Rodman Tarigan; Rini Mulia Sari; Novilia Sjafri Bachtiar; Cissy B. Kartasasmita; Kusnandi Rusmil

    In this study, we aimed to evaluate the immunological protectivity of infants following four doses of bivalent oral polio vaccine (bOPV; Bio Farma), which were given simultaneously with DTwP-Hb-Hib (Pentabio®), along with one dose of inactivated poliovirus vaccine (IPV) at the fourth visit. A total of 143 newborn infants who fulfilled the inclusion criteria were enrolled and completed the study. Subjects received the first dose of bOPV at birth. On days 60, 90 and 120, bOPV was given simultaneously with Pentabio®. On day 120, one dose of IPV was also administered. Serum samples for serology analysis were collected before the first dose of bOPV (at day 0), before the second dose of bOPV (at day 60) and 30 days after the last dose of bOPV. In addition, the intensity, duration and relationship of each adverse event to the trial vaccines were assessed. Seroprotection rates after the fourth dose of bOPV were 100%, 91.6% and 99.3% for poliovirus P1, P2 and P3, respectively. Seroconversion rates after the fourth dose of bOPV were 100.0%, 93.3% and 100% for poliovirus P1, P2 and P3, respectively. There were no severe adverse events, and systemic reactions were generally mild during the 1–28 day post-vaccination period. Collectively, our findings indicate that bOPV given simultaneously with Pentabio® and one dose of IPV at the 4th visit was immunogenic and well tolerated.

    更新日期:2020-01-23
  • Effectiveness of the current and prior influenza vaccinations in Northern Spain, 2018–2019
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Jesús Castilla; María Eugenia Portillo; Itziar Casado; Francisco Pozo; Ana Navascués; Marta Adelantado; Carlos Gómez Ibáñez; Carmen Ezpeleta; Iván Martínez-Baz

    Background The population targeted for influenza vaccination can be repeatedly vaccinated over successive seasons, and vaccines received in previous seasons may retain preventive effect. This study aims to estimate the effectiveness of inactivated influenza vaccines received in the current and prior seasons in the 2018–2019 season. Methods Influenza-like illness patients attended by sentinel general practitioners or admitted to hospitals in Navarre, Spain, were tested for influenza. Vaccination status in the current and three prior seasons was obtained from the vaccination registry. The test-negative design was used to estimate the vaccine effectiveness. Results A total of 381 influenza A(H1N1)pdm09 cases, 341 A(H3N2) cases and 1222 controls were analysed. As compared to individuals unvaccinated in the current and three prior seasons, the influenza vaccine effectiveness against A(H1N1)pdm09 was 57% (95% confidence interval [CI]: 40%, 70%) for current season vaccination regardless of prior doses and 48% (95%CI: 14%, 68%) for vaccination in prior seasons but not in the current season. These estimates were 12% (95%CI: −23%, 37%) and 27% (95%CI: −22%, 56%), respectively, against influenza A(H3N2). Individuals vaccinated with the two A(H1N1)pdm09 strains in influenza vaccines since 2009, A/Michigan/45/2015 and A/California/07/2009, had higher protection (68%; 95%CI: 53%, 77%) than those vaccinated with A/Michigan/45/2015 only (29%, p = 0.020) or with A/California/07/2009 only (34%, p = 0.005). Conclusion These results suggest moderate effectiveness of influenza vaccination against A(H1N1)pdm09 and low effectiveness against A(H3N2) influenza in the 2018–2019 season. Vaccination in prior seasons maintained a notable protective effect. Strains included in previous vaccines were as effective as the current vaccine strain, and both added their effects against influenza A(H1N1)pdm09.

    更新日期:2020-01-23
  • The history of OCV in India and barriers remaining to programmatic introduction
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Vittal Mogasale; Suman Kanungo; Sanghamitra Pati; Julia Lynch; Shanta Dutta

    Cholera-endemic Eastern India has played an important role in the development of oral cholera vaccines (OCV) through conduct of pivotal trials in Kolkata which led to the registration of the first low-cost bivalent killed whole cell OCV in India in 2009, and subsequent prequalification by the World Health Organization prequalification in 2011. Odisha hosted an influential early demonstration project for use of the vaccine in a high-risk population and provided data and lessons that were crucial input in the Vaccine Investment Strategy developed by Gavi, the Vaccine Alliance in 2013. With Gavi’s decision to finance an OCV stockpile, the demand for OCV surged and vaccine has been deployed with great success worldwide in areas of need in response to outbreaks and disasters, most notably in Africa. However, although India is considered one of the highest burden countries, no further use of OCV has occurred since the demonstration project in Odisha in 2011. In this paper we will summarize the important contributions of India to the development and use of OCV and discuss the possible barriers to OCV introduction as a public health tool to control cholera.

    更新日期:2020-01-22
  • Measles-containing vaccines in Brazil: Coverage, homogeneity of coverage and associations with contextual factors at municipal level
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Flávia C. Pacheco; Giovanny V.A. França; Guilherme A. Elidio; Mariana B. Leal; Cesar de Oliveira; Dirce B. Guilhem

    We aimed to (i) describe both the coverage and the homogeneity of coverage of the first and second doses of measles-containing vaccines (MCV) in Brazil in 2017, and (ii) to investigate the potential influence of contextual factors at municipal level. All 5570 Brazilian municipalities were included. The North and Center-West regions presented the lowest coverages of the first and second doses of MCV, respectively. We found significant associations of both first and second doses of MCV with population size, coverage of Family Health Strategy (FHS) and other indicators of living conditions and inequalities. Monitoring the homogeneity of MCV coverage at national, regional and state levels is essential, as it allows identifying areas at higher risk of measles spread that should be targeted for vaccination. Targeting large cities i.e. 100,000 or more inhabitants, especially poor neighborhoods and areas with low FHS coverage, could lead to improvements in coverage homogeneity.

    更新日期:2020-01-22
  • Propagandizing anti-vaccination: Analysis of Vaccines Revealed documentary series
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Amanda S. Bradshaw; Debbie Treise; Summer S. Shelton; Matthew Cretul; Aantaki Raisa; Alexis Bajalia; Daisha Peek
    更新日期:2020-01-22
  • Performance of the United States Vaccine Injury Compensation Program (VICP): 1988–2019
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Kimberly M. Thompson; Walter A. Orenstein; Alan R. Hinman

    The United States (US) highly values the individual and societal benefits of vaccination and invests significantly in vaccine development and use as part of its national vaccine enterprise. In 1986, recognizing the small, but non-zero risks associated with vaccines, the US created a mechanism to collect excise taxes on each dose of vaccine to fund a national Vaccine Injury Compensation Program (VICP). The VICP includes a system for those claiming serious injuries from vaccines to seek compensation, and a process to pay individuals with legitimate claims and their legal counsel. Given the maturity of the VICP, we review experience with the vaccines and injuries covered, claims, and economics of the fund. Our review shows the excellent safety track record of vaccines, provides some evidence of injuries related specifically to vaccine delivery, and discusses the financial health of the fund.

    更新日期:2020-01-22
  • Homeschooling parents in California: Attitudes, beliefs and behaviors associated with child’s vaccination status
    Vaccine (IF 3.269) Pub Date : 2020-01-22
    Salini Mohanty; Caroline M. Joyce; Paul L. Delamater; Nicola P. Klein; Daniel Salmon; Saad B. Omer; Alison M. Buttenheim

    Background Senate Bill 277 (SB277) banned nonmedical exemptions from school-entry vaccination requirements for children attending classroom-based schools in California, but excluded homeschooled children from vaccination requirements. Thus, it was hypothesized that more parents would choose to homeschool to avoid vaccination requirements in response to SB277. There is limited literature on the vaccine attitudes, beliefs, and behaviors among the homeschooling population in the US, despite an overall increase in homeschooling nationwide and documented vaccine-preventable disease outbreaks within the homeschooled child population. Methods Between November 2018 and January 2019, we conducted a cross-sectional online survey among homeschooling parents with at least one child in grades K-8 who is currently enrolled in one of the legally-acceptable mechanisms to homeschool in California: (1) home-based private school satellite program (PSP), or (2) public or charter independent study program (ISP) with no classroom-based instruction. Results Among 140 homeschooling parents from 8 schools in California, 71% reported that their youngest child in grade K-8 was up-to-date on immunizations at kindergarten-entry and 56% reported that they made the decision to homeschool their child after the implementation of SB277. Compared to homeschooling parents whose child was up-to-date at kindergarten entry, homeschooling parents whose child was not up-to-date at kindergarten entry reported higher concerns over vaccine safety and effectiveness, more frequently cited immunization mandates as a reason to homeschool, and were more likely to report having considered moving out of California due to immunization mandates. Conclusion There was variation in vaccine attitudes and beliefs within the homeschooling population in this sample. Immunization mandates were a factor in the decision to homeschool for some parents in this sample, supporting the hypothesis that vaccine-hesitant parents considered homeschooling as a way to avoid immunization mandates such as SB277. Future studies should explore the complexities around vaccine attitudes, beliefs and behaviors among homeschooling populations.

    更新日期:2020-01-22
  • School-based vaccination programmes: An evaluation of school immunisation delivery models in England in 2015/16
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    K. Tiley; E. Tessier; J.M. White; N. Andrews; V. Saliba; M. Ramsay; M. Edelstein

    Schools are increasingly being used to deliver vaccines. In 2015/16 three school-based vaccination programmes were delivered to adolescents in England: human papillomavirus (HPV), meningococcal groups A, C, W and Y disease (MenACWY) and tetanus, diphtheria and polio (Td/IPV). We assessed how school delivery models impact vaccine coverage and how a delivery model for one programme may impact another. Routinely collected national data were analysed to ascertain the school grade achieving highest coverage within each one-dose programme and to compare two-dose delivery models (within year vs across years) for the HPV vaccine. We also assessed whether the HPV delivery model was associated with coverage in other programmes. MenACWY and Td/IPV coverage was highest in younger school grades. Overall similar HPV coverage was achieved with both models (86.7% two doses within one year, 85.8% two doses across two years, p = 0.20). High two-dose HPV coverage in 2015/16 was reported in areas that achieved high HPV coverage in 2013/14 when three doses were required. Areas with high three-dose coverage in 2013/14 achieved higher coverage with a within-one-year approach (92.0% vs 85.2%, p < 0.001), whilst areas reporting low coverage in 2013/14 achieved lower but similar coverage in 2015/16 with both models (79.2% vs 80.9% p = 0.29). MenACWY and Td/IPV coverage were higher in areas with high HPV coverage in 2013/14. Among high HPV coverage areas, MenACWY coverage was higher when HPV doses were delivered within year. School-based programmes should be offered as early as feasible and acceptable to optimise coverage. The choice of delivery model for HPV should take into account local performance and provider experience. Single providers may delivery multiple vaccines and the delivery for one programme may affect the performance of other programmes. Providers should consider local circumstances including past and current vaccine coverage and factors influencing coverage when deciding what delivery model to adopt.

    更新日期:2020-01-22
  • Factors influencing Human papillomavirus (HPV) vaccination series completion in Mississippi Medicaid
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    Sushmitha Inguva; Marie Barnard; Lori M. Ward; Yi Yang; Eric Pittman; Benjamin F. Banahan; Terri R. Kirby; Sara L. Noble

    Purpose To identify factors associated with Human Papillomavirus (HPV) vaccine series completion among vaccine initiators in Mississippi Medicaid. Methods 2013–2018 Mississippi Medicaid administrative claims data were analyzed. Female and male beneficiaries aged 9 to 26 years who initiated HPV vaccination in the identification period were assessed for completion of age-appropriate number of recommended doses within a period of 12 months. Sex-stratified multivariable logistic regression was used to examine factors associated with HPV vaccine series completion in the study sample. Results A total of 18,110 female and 18,186 male beneficiaries initiated HPV vaccine between January 1, 2014 and June 30, 2017. Most of the initiators belonged to ages 11 to 12 years, African American race, managed care plans and Central Mississippi public health region. The vaccine series completion rate was 34% for females and 30% for males. Younger age at initiation was a significant predictor of vaccine series completion in both sexes. Specifically, initiators in age groups 9 to 10 and 11 to 12 years, respectively, had greater odds of completion, while initiators aged 15 to 26 years had lower odds of completion compared to initiators aged 13 to 14 years. Female and male beneficiaries in managed care plans (vs. fee-for-service) and of African American race (vs. Caucasians) had lower odds of completing the vaccine series. Female and male beneficiaries who initiated HPV vaccine series with a pediatrician had the highest completion rates. Conclusion HPV vaccination series completion rate in Mississippi Medicaid was suboptimal despite the high HPV-related cancer incidence in the state. HPV vaccine series completion is influenced by various sociodemographic factors. There is a need for robust education and public health programs to encourage completion of recommended doses.

    更新日期:2020-01-22
  • Identifying barriers and drivers to vaccination: A qualitative interview study with health workers in the Federation of Bosnia and Herzegovina
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    Sanjin Musa; Venesa Skrijelj; Aida Kulo; Katrine Bach Habersaat; Mirsad Smjecanin; Emilija Primorac; Darija Becirovic; Cath Jackson

    Background Vaccination coverage in Bosnia and Herzegovina has been declining over recent years. A World Health Organization Tailoring Immunization Programmes (TIP) project is underway to gain insights into the underlying reasons for this, to develop tailored interventions. As part of TIP, this study aimed to investigate the views of health workers on their barriers and drivers to positive childhood vaccination practices. Methods Face-to-face qualitative interviews explored 38 health workers’ views on vaccination coverage, their vaccination attitudes, and system, programme and institutional influences on their vaccination practices. The data were analysed using content analysis and organised by the COM (Capability, Opportunity and Motivation) factors. Findings Very few differences in barriers and drivers were evident between high and low coverage primary care centres or across different professional roles. Capability: Drivers included awareness of the risks of low vaccination coverage, regular use of the Rulebook and Order, knowledge of how to advise parents on mild side effects and recognition of the importance of good communication with parents. Key barriers were the use of false contraindications to postpone vacination and poor skills in tailoring communication with parents. Opportunity: Drivers were sufficient time for adminstering vaccination and good availability of vaccines. Several barriers were evident: lack of implementation of mandatory vaccination, no uniform recall and reminder system or system for detecting under-vaccinated children, staff shortages and lack of time to discuss vaccination with parents. Motivation: Drivers were a belief in the value, safety and effectiveness of vaccination and seeing that they have an important role to play. Barriers were a tendency to blame external factors e.g. anti-vax movement and a fear of being blamed for adverse events. Conclusions The study identified complex and inter-related barriers and drivers to health worker positive vaccination practices. These insights will now inform a process to identify and prioritize interventions.

    更新日期:2020-01-22
  • Genetic variability of Polish serogroup B meningococci (2010–2016) including the 4CMenB vaccine component genes
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    Izabela Waśko; Agnieszka Gołębiewska; Marlena Kiedrowska; Patrycja Ronkiewicz; Izabela Wróbel-Pawelczyk; Alicja Kuch; Eva Hong; Anna Skoczyńska

    Neisseria meningitidis serogroup B (MenB) has recently become the major cause of invasive meningococcal disease in Poland. Therefore, the purpose of this study was to characterize MenB isolates, responsible for invasive meningococcal disease in 2010–2016, by MLST and sequencing of genes encoding proteins used as 4CMenB vaccine antigens. Two methods of coverage estimation were performed: extrapolation of MATS results of Polish meningococci 2010–2011 (exMATS) and gMATS, which combines genotyping and MATS results. Among 662 isolates 20 clonal complexes (CC) were detected, of which the most frequent were CC32, CC41/44 and CC18, accounting for 31.9%, 16.5% and 12.7%, respectively. A total of 111 combinations of PorA variable regions (VR1/VR2) were found, with P1.7,16 (15.0%) and P1.22,14 (13.6%) being prevalent. Vaccine variant VR2:4 was detected in 7.3% of isolates, mainly representing CC41/44 and non-assigned CC. Eighty five fHbp alleles encoding 74 peptide subvariants were revealed. Subvariant 1.1, a component of 4CMenB, was prevalent (24.2%) and found generally in CC32. Typing of the nhba gene revealed 102 alleles encoding 87 peptides. The most frequent was peptide 3 (22.4%), whereas vaccine peptide 2 was detected in 9.8%, mostly among CC41/44. The nadA gene was detected in 34.0% of isolates and the most prevalent was peptide 1 (variant NadA-1; 71.6%), found almost exclusively in CC32 meningococci. Vaccine peptide 8 (variant NadA-2/3) was identified once. Consequently, 292 completed BAST profiles were revealed. Regarding vaccine coverage, 39.7% of isolates had at least one 4CMenB vaccine variant, but according to exMATS and gMATS the coverage was 83.3% and 86.6%, respectively. In conclusion, Polish MenB (2010–2016) was highly diverse according to MLST and gene alleles encoding 4CMenB vaccine antigens. Some correlations between clonal complexes and variants of examined proteins/BAST profiles were revealed and a high coverage of 4CMenB vaccine was estimated.

    更新日期:2020-01-22
  • An investment case for maternal and neonatal tetanus elimination
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    Sarah K. Laing; Ulla Griffiths; Azhar Abid Raza; Flint Zulu; Ahmadu Yakubu; Sophia Bessias; Sachiko Ozawa

    Introduction Globally, 13 countries have yet to eliminate maternal and neonatal tetanus. While efforts have improved access to tetanus toxoid containing vaccines (TTCVs) and increased clean delivery practices, reaching elimination targets (<1 case of neonatal tetanus per 1000 live births per district per year) may require significant resources to reach the remaining high risk and hard-to-reach districts. Methods We estimated the cost to achieve maternal and neonatal tetanus elimination (MNTE) in three years in the remaining 13 countries: Afghanistan, Angola, Central African Republic, Democratic Republic of the Congo, Guinea, Mali, Nigeria, Pakistan, Papua New Guinea, Somalia, South Sudan, Sudan, and Yemen. Costs were estimated for: (1) vaccination campaigns using standard TTCVs and TT-Uniject™ targeting women of reproductive age in high risk areas, (2) additional vaccinations delivered to pregnant women at antenatal care (ANC) clinics, (3) clean delivery and umbilical cord care promotion, (4) neonatal tetanus surveillance strengthening, and (5) validation activities. We forecasted the averted mortality to assess the cost-effectiveness of achieving MNTE. Results It will cost an estimated US$197.7 million to realize MNTE over three years. These costs include $161.4 million for vaccination campaigns, $6.1 million for routine vaccination during ANC, $23.3 million for promotion of clean delivery practices, $4 million for surveillance, and $3 million for validation of MNTE. Achieving MNTE will avert approximately 70,000 neonatal deaths over ten years of vaccine protection, resulting in approximately 4.4 million life years gained. It will cost $2,900 per death averted and $45 per life year gained. Conclusion Maternal and neonatal tetanus can be eliminated with significant financial investment, high prioritization, and strong political will. While substantial costs must be incurred to reach hard-to-reach populations, MNTE should be accomplished as a matter of health equity, and will significantly contribute to reaching the United Nations' Sustainable Development Goals.

    更新日期:2020-01-22
  • Oral cholera vaccination coverage in an acute emergency setting in Somalia, 2017
    Vaccine (IF 3.269) Pub Date : 2020-01-21
    Mutaawe Lubogo; Ahmed M. Mohamed; Abdullahi H. Ali; Aden H. Ali; Ghulam R. Popal; David Kiongo; Khalif Mohamud Bile; Mamunur Malik; Abdinasir Abubakar

    The first oral cholera vaccination (OCV) campaign in Somalia was implemented between March and October 2017. It was the first time the Ministry of Health had introduced and used OCV as part of the cholera prevention and control strategies. The Ministry of Health aimed to cover 1.1 million people ≥ 1 year with 2 doses of the OCV in 11 high-risk districts. Overall, 2-dose administrative OCV coverage in all targeted districts was 95.5%. Following the campaign, a random sample survey was conducted in 9 out of 11districts to evaluate coverage, awareness, reasons for non-vaccination, the water and sanitation status of households, and any resulting adverse events. The survey was conducted in 2 phases. Of the 3,715 eligible individuals in the first phase, 92.5% (95% CI 91.4–93.6%) received 2 doses of the OCV and 7.0% (95% CI 6.0–8.2%) 1 dose. In the second phase, of 1,926 individuals, 94.1% (95% CI 92.9–95.1%) received 2 doses and 2.6% (95% CI 2.0–3.4%) 1 dose. Despite challenges, this experience shows that OCV campaigns can be implemented in acute humanitarian settings through existing immunization structures.

    更新日期:2020-01-22
  • Porcine circovirus type 2a or 2b based experimental vaccines provide protection against PCV2d/porcine parvovirus 2 co-challenge
    Vaccine (IF 3.269) Pub Date : 2020-01-20
    Tanja Opriessnig; Anbu K. Karuppannan; Patrick G. Halbur; Jay G. Calvert; Gregory P. Nitzel; Shannon R. Matzinger; Xiang-Jin Meng

    With the discovery of Porcine circovirus type 2d (PCV2d) in the USA in 2012 and subsequent genotype shift from the previously predominant PCV2b to PCV2d in the face of widespread PCV2a vaccination, concerns over PCV2 vaccine efficacy were raised. The objective of this study was to evaluate the efficacy of two similarly produced PCV2 vaccines, one containing the PCV2a capsid and the other one containing the PCV2b capsid, in the conventional pig model against PCV2d/porcine parvovirus 2 (PPV2) co-challenge. A co-challenge was added since there is evidence that PPV2 may exacerbate PCV2 infection and since PCV2 only rarely causes disease in experimentally infected pigs, hence vaccine efficacy can be difficult to assess. In brief, sixty 3-week-old-pigs from a PCV2 seropositive farm without evidence of active virus replication (no PCV2 viremia, low antibody titers with no evidence of increase after two consecutive bleedings) were blocked by PCV2 antibody titer and then randomly divided into three groups with 20 pigs each, a non-vaccinated group (challenge control), a PCV2a vaccinated group (VAC2a) and a PCV2b vaccinated group (VAC2b). Vaccinations were done at 4 and again at 6 weeks of age. At 8 weeks of age, all pigs were challenged with a PCV2d strain via intranasal and intramuscular routes of inoculation followed by intramuscular administration of PPV2 one day later. PCV2 vaccination, regardless of PCV2 genotype, resulted in significantly higher humoral and cellular immunity compared to non-vaccinated challenge control pigs as evidenced by increased numbers of interferon (IFN) γ secreting cells after PCV2d stimulation of peripheral blood mononuclear cells collected prior to challenge. Furthermore, PCV2a and PCV2b vaccinations both reduced PCV2d viremia and PCV2-associated pathological lesions. Under the study conditions, the PCV2a and PCV2b vaccine preparations each induced immune responses and clinical protection against a heterologous PCV2d/PPV2 co-challenge.

    更新日期:2020-01-21
  • Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting
    Vaccine (IF 3.269) Pub Date : 2020-01-20
    Amanda J. Driscoll; S. Hasan Arshad; Louis Bont; Steven M. Brunwasser; Thomas Cherian; Janet A. Englund; Deshayne B. Fell; Laura L. Hammitt; Tina V. Hartert; Bruce L. Innis; Ruth A. Karron; Gayle E. Langley; E. Kim Mulholland; Patrick K. Munywoki; Harish Nair; Justin R. Ortiz; David A. Savitz; Nienke M. Scheltema; Daniel R. Feikin

    Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12–13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.

    更新日期:2020-01-21
  • Who is at risk of 13-valent conjugated pneumococcal vaccine failure?
    Vaccine (IF 3.269) Pub Date : 2020-01-20
    Melike Yildirim; Pinar Keskinocak; Stephen Pelton; Larry Pickering; Inci Yildirim

    Background Despite high vaccine coverage rates in children and efficacy of pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) episodes due to serotypes included in the vaccine following completion of the recommended course of immunisation (i.e. vaccine failure) have been reported. Methods We used data gathered from a population-based enhanced passive surveillance for IPD in children under 18 years of age in Massachusetts and an ensemble model composed of three machine-learning algorithms to predict probability of 13-valent pneumococcal conjugated vaccine (PCV13) failure and to evaluate potential associated features including age, underlying comorbidity, clinical presentation, and vaccine schedule. Vaccine failure was defined as diagnosis of IPD due to vaccine serotype (VST), in a child who received age recommended doses recommended by Advisory Committee of Immunization Practices. Results During the 7-year study period, between April 01, 2010 and March 31, 2017, we identified 296 IPD cases. There were 107 (36%) IPD cases caused by VST, mostly serotype 19A (49, 17%), 7F (21, 7%), and 3 (18, 6%). Thirty-seven (34%) were in children who were completely vaccinated representing 13% of all IPD cases. Vaccine failure was more likely among children older than 60 months (predicted probability 0.40, observed prevalence 0.37, model prediction accuracy 79%), children presenting with pneumonia (predicted probability 0.27, observed prevalence 0.31, model accuracy 77%), and children with underlying comorbidity (predicted probability 0.24, observed prevalence 0.23, model accuracy 96%). Vaccine failure probability for those >60 months of age and had an underlying risk factor was 45% (observed prevalence 0.33, model accuracy 82%). The likelihood of vaccine failure was lowest among children who had completed 3 primary doses plus one booster dose PCV13 (predicted probability 0.14, observed prevalence 0.14, model prediction accuracy 100%). Conclusion PCV13 vaccine failure is more frequent among older children with underlying comorbidity, and among those who present with pneumococcal pneumonia. Our study provides a preliminary framework to predict the patterns of vaccine failures and may contribute to decision-making processes to optimize PCV immunization schedules.

    更新日期:2020-01-21
  • Opportunities for an atherosclerosis vaccine: From mice to humans
    Vaccine (IF 3.269) Pub Date : 2020-01-19
    Payel Roy; Amal J. Ali; Kouji Kobiyama; Yanal Ghosheh; Klaus Ley

    Atherosclerosis, the major underlying cause of cardiovascular diseases (CVD), is the number one killer globally. The disease pathogenesis involves a complex interplay between metabolic and immune components. Although lipid-lowering drugs such as statins curb the risks associated with CVD, significant residual inflammatory risk remains. Substantial evidence from experimental models and clinical studies has established the role of inflammation and immune effector mechanisms in the pathogenesis of atherosclerosis. Several stages of the disease are affected by host-mediated antigen-specific adaptive immune responses that play either protective or proatherogenic roles. Therefore, strategies to boost an anti-atherogenic humoral and T regulatory cell response are emerging as preventative or therapeutic strategies to lowering inflammatory residual risks. Vaccination holds promise as an efficient, durable and relatively inexpensive approach to induce protective adaptive immunity in atherosclerotic patients. In this review, we discuss the status and opportunities for a human atherosclerosis vaccine. We describe (1) some of the immunomodulatory therapeutic interventions tested in atherosclerosis (2) the immune targets identified in pre-clinical and clinical investigations (3) immunization strategies evaluated in animal models (4) past and ongoing clinical trials to examine the safety and efficacy of human atherosclerosis vaccines and (5) strategies to improve and optimize vaccination in humans (antigen selection, formulation, dose and delivery).

    更新日期:2020-01-21
  • Subcutaneous vaccination with a live attenuated Yersinia pseudotuberculosis plague vaccine
    Vaccine (IF 3.269) Pub Date : 2020-01-18
    Anne Derbise; Chloé Guillas; Christiane Gerke; Elisabeth Carniel; Javier Pizarro-Cerdà; Christian E. Demeure

    A single oral inoculation to mice of the live attenuated Yersinia pseudotuberculosis VTnF1 strain producing an F1 pseudocapsule protects against bubonic and pneumonic plague. However oral vaccination can fail in humans exposed to frequent intestinal infections. We evaluated in mice the efficacy of subcutaneous vaccine injection as an alternative way to induce protective immunity, while reducing the dose and avoiding strain release in nature. A single subcutaneous dose of up to 108 CFU induced dose-dependent antibody production. At the dose of 107 CFU, i.e. 10 times less than via the oral route, it caused a modest skin reaction and protected 100% against bubonic and 80% against pneumonic plague, caused by high doses of Yersinia pestis. Bacteria migrating to lymph nodes and spleen, but not feces, were rapidly eliminated. Thus, subcutaneous injection of VTnF1 would represent a good alternative when dissemination in nature and human intestinal responsiveness are limitations.

    更新日期:2020-01-21
  • Thin silk fibroin films as a dried format for temperature stabilization of inactivated polio vaccine
    Vaccine (IF 3.269) Pub Date : 2020-01-17
    Jordan A. Stinson; Carter R. Palmer; David P. Miller; Adrian B. Li; Kandice Lightner; Heather Jost; William C. Weldon; M. Steven Oberste; Jonathan A. Kluge; Kathryn M. Kosuda

    Current inactivated polio vaccine (IPV) products are sensitive to both freezing and elevated temperatures and therefore must be shipped and stored between 2 °C and 8 °C, a requirement that imposes financial and logistical challenges for global distribution. As such, there is a critical need for a robust, thermally stable IPV to support global polio eradication and post-eradication immunization needs. Here, we present the development of air-dried thin films for temperature stabilization of IPV using the biomaterial silk fibroin. Thin-film product compositions were optimized for physical properties as well as poliovirus D-antigen recovery and were tested under accelerated and real-time stability storage conditions. Silk fibroin IPV films maintained 70% D-antigen potency after storage for nearly three years at room temperature, and greater than 50% potency for IPV-2 and IPV-3 serotypes at 45 °C for one year. The immunogenicity of silk fibroin IPV films after 2-week storage at 45 °C was assessed in Wistar rats and the stressed films generated equivalent neutralizing antibody responses to commercial vaccine for IPV-1 and IPV-2. However, the absence of IPV-3 responses warrants further investigation into the specificity of ELISA for intact IPV-3 D-antigen. By demonstrating immunogenicity post-storage, we offer the air-dried silk film format as a means to increase IPV vaccine access through innovative delivery systems such as microneedles.

    更新日期:2020-01-17
  • Development and optimization of OspC chimeritope vaccinogens for Lyme disease
    Vaccine (IF 3.269) Pub Date : 2020-01-17
    Jerilyn R. Izac; Nathaniel S. O'Bier; Lee D. Oliver; Andrew C. Camire; Christopher G. Earnhart; DeLacy V. LeBlanc Rhodes; Brandon F. Young; Stuart R. Parnham; Christopher Davies; Richard T. Marconi

    Experimental Outer surface protein (Osp) C based subunit chimeritope vaccinogens for Lyme disease (LD) were assessed for immunogenicity, structure, ability to elicit antibody (Ab) responses to divergent OspC proteins, and bactericidal activity. Chimeritopes are chimeric epitope based proteins that consist of linear epitopes derived from multiple proteins or multiple variants of a protein. An inherent advantage to chimeritope vaccinogens is that they can be constructed to trigger broadly protective Ab responses. Three OspC chimeritope proteins were comparatively assessed: Chv1, Chv2 and Chv3. The Chv proteins possess the same set of 18 linear epitopes derived from 9 OspC type proteins but differ in the physical ordering of epitopes or by the presence or absence of linkers. All Chv proteins were immunogenic in mice and rats eliciting high titer Ab. Immunoblot and enzyme linked immunosorbent assays demonstrated that the Chv proteins elicit IgG that recognizes a diverse array of OspC type proteins. The panel included OspC proteins produced by N. American and European strains of the LD spirochetes. Rat anti-Chv antisera uniformly labeled intact, non-permeabilized Borreliella burgdorferi demonstrating that vaccinal Ab can bind to targets that are naturally presented on the spirochete cell surface. Vaccinal Ab also displayed potent complement dependent-Ab mediated killing activity. This study highlights the ability of OspC chimeritopes to serve as vaccinogens that trigger potentially broadly protective Ab responses. In addition to the current use of an OspC chimeritope in a canine LD vaccine, chimeritopes can serve as key components of human LD subunit vaccines.

    更新日期:2020-01-17
  • Women who received varicella vaccine versus natural infection have different long-term T cell immunity but similar antibody levels
    Vaccine (IF 3.269) Pub Date : 2020-01-17
    Ellen Tourtelot; Sally Quataert; J. Christopher Glantz; Lauren Perlis; Gowrishankar Muthukrishnan; Tim Mosmann

    Background Varicella-zoster virus (VZV) infection during pregnancy is associated with serious fetal anomalies. The live-attenuated VZV vaccine was approved in 1995, so many vaccinated women are now of childbearing age. The question of long-term immunity to varicella is critical because breakthrough chickenpox can occur after vaccination. Objective To compare humoral and T cell immunity between women of childbearing age who were immunized by vaccination or chickenpox disease. Study design Non-pregnant females between 18 and 36 years old with a history of VZV immunization (n = 20) or prior chickenpox disease (n = 20) were recruited. IgG antibody titers and T cell responses were measured by flow cytometry-based methods in serum and peripheral blood, respectively. Results There were no significant differences in median antibody titers between vaccinated and chickenpox groups (p = 0.34). The chickenpox group had significantly higher levels of VZV antigen-specific CD4 T cells (p = 0.004). Conclusion Natural infection induced higher VZV-specific T cell immune responses than vaccination.

    更新日期:2020-01-17
  • Activity of human serum antibodies in an influenza virus hemagglutinin stalk-based ADCC reporter assay correlates with activity in a CD107a degranulation assay
    Vaccine (IF 3.269) Pub Date : 2020-01-17
    Veronika Chromikova; Jessica Tan; Sadaf Aslam; Arvind Rajabhathor; Maria Bermudez-Gonzalez; Juan Ayllon; Viviana Simon; Adolfo García-Sastre; Bruno Salaun; Raffael Nachbagauer; Florian Krammer

    The stalk of the influenza virus hemagglutinin (HA) is an attractive target for antibody-based universal influenza virus vaccine development. While antibodies that target this part of the virus can be neutralizing, it has been shown in recent years that Fc receptor-mediated effector functions are of significant importance for the protective effect of anti-stalk antibodies. Several assays to measure Fc-Fc receptor interaction-based effector functions like antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis exist, but they suffer from limitations such as low throughput and high run-to-run variability. Reporter assays for antibody-dependent cellular cytotoxicity based on reporter cells that express luciferase upon engagement of human FcγRIIIa with the Fc of antigen-bound antibodies have been developed as well. These reporter assays can be used in a higher throughput setting with limited run-to-run assay variability but since they express only one Fc receptor, their biological relevance is unclear. Here we optimized an antibody-dependent cellular cytotoxicity reporter assay to measure the activity of antibodies to the conserved stalk domain of H1 hemagglutinin. The assay was then correlated to a CD107a-based degranulation assay, and a strong and significant correlation could be observed. This data suggests that the FcγRIIIa-based reporter assay is a good substitute for functional assays, especially in settings where larger sample numbers need to be analyzed.

    更新日期:2020-01-17
  • Cross-sectional study of hepatitis B antibody status in health care workers immunized as children at an academic medical center in Wisconsin
    Vaccine (IF 3.269) Pub Date : 2020-01-16
    Alicia M. Ritscher; Megan LeClair-Netzel; Nicholas J. Friedlander; Danielle N. Howard Stewart; Mallory Wagner; Nicole Kalscheur; Freddy Caldera; Mary S. Hayney

    Individuals who received the hepatitis B vaccine series as young children are entering the healthcare workforce. Our study measured the persistence of antibody to the hepatitis B surface antigen (anti-HBs) at time of employment. Among 986 individuals born in 1991 or more recently with documentation of completion of the hepatitis B vaccine series, 51% had anti-HBs < 10mIU/ml. Of these 507 healthcare workers, 446 (88%) received documented fourth dose of hepatitis B vaccine followed by another anti-HBs ≥ 28 days post vaccination; 11% (50/446 or 5% of the total population) did not mount an anamnestic response. The non-responders were more likely to be male or complete the vaccine series prior to age 7 months. Measuring anti-HBs at the time of hire in this population of healthcare workers who had documentation of hepatitis B series completion as young children may be unnecessary because of the high rate of hepatitis B vaccine protection.

    更新日期:2020-01-16
  • Evaluation of Japanese encephalitis virus E and NS1 proteins immunogenicity using a recombinant Newcastle disease virus in mice
    Vaccine (IF 3.269) Pub Date : 2020-01-16
    Barnali Nath; Vandna; Hari Mohan Saini; Minakshi Prasad; Sachin Kumar

    Japanese encephalitis (JE) is the most important cause of acute encephalitis syndrome (AES). Japanese encephalitis virus (JEV), the prototype member of the JE serocomplex, belongs to the genus Flavivirus. The immunogenic proteins envelope (E) and non-structural protein 1 (NS1) of JEV are widely explored for the development of vaccines and diagnostics against JEV. However, there are underlying concerns such as the risk of reversion of live-attenuated vaccines to high virulence, the incomplete inactivation of pathogens in inactivated vaccines and partial vaccine coverage. Newcastle disease virus (NDV) is an efficient viral vaccine vector to express several human and animal immunogenic proteins. In the present study, we have developed a recombinant NDV (rNDV), individually expressing the E and NS1 proteins of JEV (rNDV-Ejev and rNDV-NS1jev). The recovered rNDV-Ejev and rNDV-NS1jev were characterized in 9-day-old SPF embryonated chicken eggs and in cell culture. The vaccination of rNDV-Ejev and rNDV-NS1jev showed effective immunity against JEV upon intranasal immunization in BALB/c mice. The rNDVs vaccination produced effective neutralization antibody titers against both NDV and JEV. The cytokine profiling of the vaccinated mice showed an effective Th1 and Th2 mediated immune response. The study also provided an insight that E, when used in combination with NS1 could reduce the efficacy of only E based immunization in mice. Our results suggested rNDV-Ejev to be a promising live viral vectored vaccine against JEV. This study implies an alternative and economical strategy for the development of a recombinant vaccine against JEV.

    更新日期:2020-01-16
  • Meeting report: WHO consultation on accelerating Lassa fever vaccine development in endemic countries, Dakar, 10–11 September 2019
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Kolawole Salami; Pierre-Stéphane Gsell; Adebola Olayinka; Diadie Maiga; Pierre Formenty; Peter G. Smith; Vasee Moorthy

    At the time of writing in 2019, there have been 754 confirmed cases of Lassa fever in Nigeria, 21% of whom have died. Lassa is on the priority pathogen list for WHO’s R&D Blueprint for Action to Prevent Epidemics. In September 2019, WHO convened 67 scientists, regulators, ethicists, public health officials, funders and vaccine developers to discuss the end-to-end clinical development plan for Lassa fever vaccines. The substantial increases in vaccine trial capacity in Africa were reviewed, together with lessons learned from the evaluation of vaccines against HIV, TB, malaria, and Ebola in Africa. Participants agreed on a pathway for Lassa vaccine trial progression, as outlined in WHO’s Lassa fever R&D roadmap and the WHO Lassa fever Target Product Profile. Two Phase 1 trials of Lassa vaccines have already started, and it was agreed that continuing interactions between high income and African regulatory and ethics authorities and WHO will be important in progression towards Phase 2b/3 efficacy trials in Lassa fever endemic areas. There was agreement that, for diseases whose burden is mainly in Africa, it should be the norm that African regulatory authorities are consulted on trial design/progression before first-in-human Phase 1 trials. Phase 2b-3 vaccine trial capacity needs to be in place in high Lassa fever burden areas where efficacy trials will take place. Licensure of one or more Lassa fever vaccines suitable for West African populations is a realistic goal in the next 5 years, with CEPI and WHO aligned on the pathway forward for vaccine development.

    更新日期:2020-01-15
  • Safety of tetanus, diphtheria, and acellular pertussis vaccination among pregnant active duty U.S. military women
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Clinton Hall; Lisa M. Abramovitz; Anna T. Bukowinski; Ashley A. Ricker; Zeina G. Khodr; Gia R. Gumbs; Natalie Y. Wells; Ava Marie S. Conlin

    Background The tetanus, diphtheria, and acellular pertussis (Tdap) vaccine was approved for U.S. adults in 2005 and recommended for administration in every pregnancy in 2012, with optimal timing between 27 and 36 weeks’ gestation. In the military, however, a current Tdap vaccination status is compulsory for service, and active duty women may be inadvertently exposed in early pregnancy. Safety data in this population are limited. Objectives To assess safety of inadvertent (0–13 weeks’ gestation) and recommended (27–36 weeks’ gestation) exposure to the Tdap vaccine in pregnancy. Methods Pregnancies and live births from Department of Defense Birth and Infant Health Research program data were linked with military personnel immunization records to determine pregnancy Tdap vaccine exposure among active duty women, 2006–2014. Multivariable Cox and generalized linear regression models estimated associations between Tdap vaccine exposure and adverse pregnancy or infant outcomes. Results Of 145,883 pregnancies, 1272 were exposed to the Tdap vaccine in the first trimester and 9438 between 27 and 36 weeks’ gestation. Neither inadvertent nor recommended vaccine exposure were associated with spontaneous abortion, preeclampsia, or preterm labor. Among 117,724 live born infants, 984 were exposed to the Tdap vaccine in the first trimester and 9352 between 27 and 36 weeks’ gestation. First trimester exposure was not associated with birth defects, growth problems in utero, growth problems in infancy, preterm birth, or low birth weight. Tdap vaccine exposure between 27 and 36 weeks’ gestation was not associated with any adverse infant outcome. Conclusions Among a population of active duty women in the U.S. military who received the Tdap vaccine during pregnancy, we detected no increased risks for adverse maternal, fetal, or infant outcomes. Our findings corroborate existing literature on the safety of exposure to the Tdap vaccine in pregnancy.

    更新日期:2020-01-15
  • Comparison of hepatitis B surface antibody levels induced by the pentavalent DTwP-HB-Hib versus the hexavalent DTaP-HB-Hib-IPV vaccine, administered to infants at 2, 4, 6, and 18 months of age, following monovalent hepatitis B vaccination at birth
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Nawarat Posuwan; Nasamon Wanlapakorn; Sompong Vongpunsawad; Palittiya Sintusek; Elke Leuridan; Pierre Van Damme; Yong Poovorawan

    Background In Thailand, the hepatitis B (HB) vaccine is administered as a tetravalent vaccine (DTwP-HB) to all infants at 2, 4, and 6 months of age, following an initial vaccination with a monovalent HB vaccine at birth. As part of ongoing vaccine evaluation, we aimed to compare the hepatitis B immunogenicity profiles of children who had received either the pentavalent (DTwP-HB-Hib) or the hexavalent (DTaP-HB-Hib-IPV) vaccine. Methods Two groups of infants, whose mothers previously received the tetanus-diphtheria-acellular pertussis vaccine (Tdap), were randomly vaccinated with either pentavalent or hexavalent vaccine at 2, 4, 6, and 18 months of age, following monovalent HB vaccine at birth. Blood samples were obtained at birth, one-month post-primary series immunization (mo 7), pre-booster (mo 18), one-month post-booster (mo 19), and six months post-booster (mo 24). The third group of infants, whose mothers did not receive Tdap, was vaccinated with DTwP-HB-Hib (EPI pentavalent group). Levels of HBsAg, anti-HBc, and anti-HBs were evaluated by means of an automated Chemiluminescent Microparticle Immunoassay. Results Anti-HBs levels of ≥10 mIU/ml were achieved in 99.2% (hexavalent group), 99.2% (pentavalent group), and 98.5% (EPI pentavalent group) of infants, after four-dose immunization (at 0, 2, 4, 6 months of age). One month after the additional dose given at 18 months of age, anti-HBs levels of ≥10 mIU/ml were observed in 100% (hexavalent group), 99.2% (pentavalent group), and 93.8% (EPI pentavalent group) of infants. At 24 months of age, higher percentages of infants achieving anti-HBs levels ≥10 mIU/ml were found in the hexavalent group (98.3%) compared to the pentavalent group (86.5%). Conclusions Both vaccines were effective in inducing anti-HBs levels of ≥10 mIU/ml, and therefore either can be used as a single formula booster at 18 months of age to simplify vaccine administration under the Expanded Program on Immunization in Thailand.

    更新日期:2020-01-15
  • Protection of chickens against hepatitis-hydropericardium syndrome and Newcastle disease with a recombinant Newcastle disease virus vaccine expressing the fowl adenovirus serotype 4 fiber-2 protein
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Kai-yue Tian; Hui-Fang Guo; Ning Li; Yu-han Zhang; Zeng Wang; Baiyu Wang; Xia Yang; Yong-tao Li; Jun Zhao

    Newcastle disease (ND) is one of the most important and devastating avian diseases with considerable threat to the global poultry industry. Hepatitis-hydropericardium syndrome (HHS), caused by virulent fowl adenovirus serotype 4 (FAdV-4), is another highly infectious disease in chickens with severe economic impact. The effective way to combat ND and HHS is by vaccinating the poultry. In the present study, a recombinant NDV LaSota vaccine strain expressing full length fiber-2 gene of FAdV-4 (rLaSota-fiber2) was generated using reverse genetics. The FAdV-4 fiber-2 protein was expressed as a soluble form rather than NDV membrane-anchored form. The rLaSota-fiber2 was genetically stable, and it showed growth patterns in embryonated eggs comparable to that of parental rLaSota virus. Since our unpublished data demonstrated that delivery of live rLaSota-fiber2 in drinking water or ocular delivery of the vaccine didn’t produce protection against hypervirulent FAdV-4 challenge, even though the vaccine provide full protection against NDV challenge, the efficacy of the rLaSota-fiber2 was evaluated by delivering the vaccine intramuscularly in this study. Single-dose intramuscular vaccination of 2-week-old SPF White Leghorn chicks with the live or inactivated rLaSota-fiber2 provided complete protection against virulent NDV challenge. However, single-dose intramuscular vaccination with the live rLaSota-fiber2 vaccine provided better protection against virulent FAdV-4 challenge and significantly reduced faecal viral shedding comparing to the inactivated vaccine. These results indicate that the NDV-vectored FAdV-4 vaccine is a promising bivalent vaccine candidate to control both HHS and ND.

    更新日期:2020-01-14
  • Decreased ratio of influenza-specific IgG versus IgM in response to influenza vaccination in antiretroviral-treated HIV-infected African Americans compared to Caucasians, and its direct correlation with the percentages of peripheral Tfh cells
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Ping Ma; Zhenwu Luo; Jing Qian; Zhongfang Yan; Lumin Zhang; Lisa Martin; Ziyu Wang; Huan Xia; Fangfang Yu; Wei Jiang

    Background Racial differences have been observed in the rate of bacterial infection and disease progression in HIV. Here, we evaluate racial differences in seasonal influenza vaccine responses. Methods 16 healthy controls (9 Caucasians (CC) and 7 African Americans (AA)) and 26 antiretroviral therapy (ART)-treated aviremic HIV+ subjects (11 CC and 15 AA) were enrolled in the current study. Blood was collected at pre-vaccination (D0) and day 14 (D14) following seasonal influenza vaccination. Serologic responses were characterized in plasma by ELISA. B and T cells were assessed by flow cytometry ex vivo. Results The absolute counts of CD4+ CD3+ T cells and CD19+ B cells were similar in healthy controls and HIV-infected individuals, and similar in CC and AA in the two study groups. However, the percentage of peripheral T follicular helper (pTfh) cells was decreased in HIV+ AA compared to HIV+ CC. There were no racial differences in IgG antibody responses against vaccination in the two study groups. However, the ratio of anti-influenza-specific IgG versus IgM induction following vaccination was decreased in HIV+ AA compared to HIV+ CC, which was directly correlated with the percentages of pTfh cells. This racial difference and correlation were not demonstrable in healthy controls. Conclusion Here we report that HIV + AA has decreased fold induction of IgG versus IgM after influenza vaccination, which may suggest impaired class-switching from IgM to IgG in AA HIV-infected individuals.

    更新日期:2020-01-14
  • Comparison of the immunogenicity and safety of quadrivalent and tetravalent influenza vaccines in children and adolescents
    Vaccine (IF 3.269) Pub Date : 2020-01-14
    Chenyang Huang; Xiaofang Fu; Yuqing Zhou; Fenfang Mi; Guo Tian; Xiaoxiao Liu; Jie Wu; Cheng Ding; Danying Yan; Lanjuan Li; Shigui Yang

    Background Children and adolescents are susceptible to influenza. Vaccination is the most important strategy for preventing influenza, yet there are few studies on the immunogenicity and safety of quadrivalent inactivated influenza vaccine (QIV) containing two A strains (H1N1 and H3N2) and two B lineages (Victoria and Yamagata). Therefore, to further clarify the immunogenicity and safety of QIV in children and adolescents, a meta-analysis was performed to provide a reference for the development of influenza prevention strategies. Methods PubMed, EMBASE and Cochrane Library were searched for articles published as of February 12, 2019. Random clinical trials comparing the immunogenicity and safety of QIV and TIV among children and adolescents were selected. The main outcomes were comparisons of immunogenicity (seroprotection rate [SPR] and seroconversion rate [SCR] and adverse events using risk ratios (RRs). The meta-analysis was performed using random-effects models. Results Among the 6 months up to 3 years group, QIV showed a higher SPR for B lineages than for TIV-B/Yamagata, with pooled RRs of 3.07 (95% CI: 2.58–3.66) and 1.06 (95% CI: 1.01–1.11), respectively. For the 3 years through 18 years, QIV had a higher SCR and SPR for the Yamagata lineage than for TIV-B/Victoria, with pooled RRs of 2.30 (95% CI: 1.83–2.88) and 1.16 (95% CI: 1.03–1.30), respectively. Compared to TIV-B/Yamagata, a higher SCR and SPR for the Victoria lineage was found for QIV, with RRs of 3.09 (95% CI: 1.99–4.78) and 1.72 (95% CI: 1.22–2.41), respectively. Regarding adverse events, only pain was more frequently reported for QIV than TIV ; the RR was 1.09 (95% CI: 1.02–1.17). Conclusions The immunogenicity of QIV for common ingredients was similar to that of TIV, but the former exhibited significantly higher immunogenicity for the unique lineage. QIV also had the same reliable safety as TIV.

    更新日期:2020-01-14
  • Characterization of thermostable Newcastle disease virus recombinants expressing the hemagglutinin of H5N1 avian influenza virus as bivalent vaccine candidates
    Vaccine (IF 3.269) Pub Date : 2020-01-11
    Lulai Xu; Zhenqiao Qin; Lei Qiao; Jie Wen; Huabin Shao; Guoyuan Wen; Zishu Pan

    Newcastle disease virus (NDV) has been used as a vector in the development of vaccines and gene delivery. In the present study, we generated the thermostable recombinant NDV (rNDV) expressing the different forms of hemagglutinin (HA) of highly pathogenic avian influenza virus (HPAIV) H5N1 based on the full-length cDNA clone of thermostable TS09-C strain. The recombinant thermostable Newcastle disease viruses, rTS-HA, rTS-HA1 and rTS-tPAs/HA1, expressed the HA, HA1 or modified HA1 protein with the tissue plasminogen activator signal sequence (tPAs), respectively. The rNDVs displayed similar thermostability, growth kinetics and pathogenicity compared with the parental TS09-C virus. The tPAs facilitated the expression and secretion of HA1 protein in cells infected with rNDV. Animal studies demonstrated that immunization with rNDVs elicited effective H5N1- and NDV-specific antibody responses and conferred immune protection against lethal H5N1 and NDV challenges in chickens and mice. Importantly, vaccination of rTS-tPAs/HA1 resulted in enhanced protective immunity in chickens and mice. Our study thus provides a novel thermostable NDV-vectored vaccine candidate expressing a soluble form of a heterologous viral protein, which will greatly aid the poultry industry in developing countries.

    更新日期:2020-01-13
  • Comparison of alpha-spending plans for near real-time monitoring for Guillain-Barré after influenza vaccination during the 2010/11 influenza season
    Vaccine (IF 3.269) Pub Date : 2020-01-10
    Sukhminder K. Sandhu; Wei Hua; Thomas E. MaCurdy; Riley L. Franks; Armen Avagyan; Yoganand Chillarige; Michael Wernecke; Jeffrey Kelman; Robert Ball

    Background Near real-time surveillance of the influenza vaccine, which is administered to a large proportion of the US population every year, is essential to ensure safety of the vaccine. For efficient near real-time surveillance, it is key to select appropriate parameters such as monitoring start date, number of interim tests and a scheme for spending a pre-defined total alpha across the entire influenza season. Guillain-Barré Syndrome, shown to be associated with the 1976 influenza vaccine, is used to evaluate how choices of these parameters can affect whether or not a signal is detected and the time to signal. FDA has been monitoring for the risk of GBS after influenza vaccination for every influenza season since 2008. Methods Using Medicare administrative data and the Updating Sequential Probability Ratio Test methodology to account for claims delay, we evaluated a number of different alpha-spending plans by varying several parameters. Results For relative risks of 5 or greater, almost all alpha-spending plans have 100% power; however, for relative risks of 1.5 or lower, the constant and O’Brien-Fleming plans have increasingly more power. For RRs of 1.5 and greater, the Pocock plan signals earliest but would not signal at a RR of 1.25, as observed in prior influenza seasons. There were no remarkable differences across the different plans in regards to monitoring start dates defined by the number of vaccinations; reducing the number of interim tests improves performance only marginally. Conclusions A constant alpha-spending plan appears to be robust, in terms of power and time to detect a signal, across a range of these parameters, including alternate monitoring start dates based on either cumulative vaccinations or GBS claims observed, frequency of monitoring, hypothetical relative risks, and vaccine uptake patterns.

    更新日期:2020-01-11
  • Mucosal delivery of live Lactococcus lactis expressing functionally active JlpA antigen induces potent local immune response and prevent enteric colonization of Campylobacter jejuni in chickens
    Vaccine (IF 3.269) Pub Date : 2020-01-10
    Chandan Gorain; Ankita Singh; Sudipta Bhattacharyya; Anirban Kundu; Aritraa Lahiri; Subhadeep Gupta; Amirul I. Mallick

    Successful colonization of the mucosal epithelial cells is the key early step for Campylobacter jejuni (C. jejuni) pathogenesis in humans. A set of Surface Exposed Colonization Proteins (SECPs) are known to take leading role in bacterial adhesion and subsequent host pathogenesis. Among the major SECPs, the constitutively expressed C. jejuni surface lipoprotein Jejuni lipoprotein A (JlpA), interacts with intestinal heat shock protein 90α (Hsp90α) and contributes in disease progression by triggering pro-inflammatory responses via activation of NF-κB and p38 MAP kinase pathways. In addition to its ability to express on the surface, high sequence conservation of JlpA protein among different Campylobacter spp make it a suitable vaccine target against C. jejuni. Given that chickens are the primary source for C. jejuni infection in humans and persistent cecal colonization significantly contribute in pathogen transmission, we explicitly used chickens as a model to test the immune-protective efficacy of JlpA protein. Taking into account that gastro-intestinal tract is the major site for C. jejuni colonization, we chose to use mucosal (intragastric) route as mode for JlpA antigen delivery. To deliver JlpA via mucosal route, we engineered a food grade Lactic acid producing bacteria, Lactococcus lactis (L. lactis) to express functionally active JlpA protein in the surface. Further, we demonstrated its ability to substantially improve the antigen specific local immune responses in the intestine along with significant immune-protection against enteric colonization of C. jejuni in chickens.

    更新日期:2020-01-11
  • Population seroprotection against hepatitis a virus in Israel 18 years after introduction of inactivated vaccine into the routine childhood vaccination schedule
    Vaccine (IF 3.269) Pub Date : 2020-01-10
    Inbal Galor; Michal Perry Markovich; Dana Wolf; Meital Haber; Michael Hartal; Eva Avramovich

    Vaccine against Hepatitis A virus (HAV) is part of the routine vaccination schedule in Israel since 1999. As of 2016, new recruits to the Israel Defense Forces should have been vaccinated in their childhood. This sero-survey aimed to determine immunity against HAV 18 years after childhood vaccination, and to re-evaluate the need for HAV vaccination booster upon recruitment. Two populations were studied: soldiers who were recruited during 2011–2012, who belonged to birth cohorts before childhood vaccination (BCV) was introduced; and recruits from 2017, who belonged to birth cohorts after childhood vaccination (ACV) was introduced. Data on 339 BCV recruits and 295 ACV recruits were analyzed. Seropositivity was 35% in the BCV group and 68% in the ACV group (P < 0.0001). Seropositivity rates among ACV subjects enable evaluation of the vaccination program’s impact on the population. Our findings do not support discontinuation of HAV vaccination of at risk groups until further evaluation.

    更新日期:2020-01-11
  • The effectiveness of influenza vaccination in pregnancy in relation to child health outcomes: Systematic review and meta-analysis
    Vaccine (IF 3.269) Pub Date : 2020-01-10
    J.R. Jarvis; R.B. Dorey; F.D.M. Warricker; N.A. Alwan; C.E. Jones

    Objectives To determine the effectiveness of influenza vaccination during pregnancy on child health outcomes. Design Systematic review/meta-analysis. Data sources Clinical Trials.gov, Cochrane Library, EMBASE, Medline, Medline in process, PubMed and Web of Science, from 1st January 1996 to 29th June 2018. An updated Medline search was performed 30th June 2018 to 31st October 2019. Methods Randomised controlled trials (RCTs) and observational studies reporting health outcomes of infants and children born to women who received inactivated influenza vaccine during pregnancy. The primary outcome was infant laboratory confirmed influenza (LCI). Secondary outcomes included influenza-like illness (ILI), other respiratory illnesses, primary care, clinic visit or hospitalisations due to influenza illness and long-term respiratory childhood outcomes. Results 19 studies were included; 15 observational studies and 4 primary RCTs with an additional 3 papers reporting secondary outcomes of these RCTs. In a random effects meta-analysis of 2 RCTs including 5742 participants, maternal influenza vaccination was associated with an overall reduction of LCI in infants of 34% (95% confidence interval 15–50%). However, there was no effect of maternal influenza vaccination on ILI in infants ≤6 months old. Two RCTs were excluded from the meta-analysis for the outcome of LCI in infants (different controls used). Both of these studies showed a protective effect for infants from LCI, with a vaccine efficacy of up to a 70%. Overall observational studies showed an inverse (protective) association between maternal influenza vaccination and infant LCI, hospitalisation and clinic visits due to LCI or ILI in infants and other respiratory illness in infants ≤6 months old. Conclusions This systematic review supports maternal influenza vaccination as a strategy to reduce LCI and influenza-related hospitalisations in young infants. Communicating these benefits to pregnant women may support their decision to accept influenza vaccination in pregnancy and increase vaccine coverage in pregnant women. Registration PROSPERO CRD42018102776.

    更新日期:2020-01-11
  • Persistence of vaccine-elicited immune response up to 14 years post-HIV gp120-NefTat/AS01B vaccination
    Vaccine (IF 3.269) Pub Date : 2020-01-10
    Olivier Van Der Meeren; Erik Jongert; Kelly E. Seaton; Marguerite Koutsoukos; Annelies Aerssens; Caroline Brackett; Muriel Debois; Michel Janssens; Geert Leroux-Roels; Doris Mesia Vela; Sheetal Sawant; Nicole L. Yates; Georgia D. Tomaras; Isabel Leroux-Roels; François Roman

    Background Vaccines eliciting protective and persistent immune responses against multiple human immunodeficiency virus type 1 (HIV-1) clades are needed. This study evaluated the persistence of immune responses induced by an investigational, AS01-adjuvanted HIV-1 vaccine as long as 14 years after vaccination. Methods This phase I, open-label, descriptive, mono-centric, extension study with a single group (NCT03368053) was conducted in adults who received ≥3 doses of the clade B gp120-NefTat/AS01B vaccine candidate 14 years earlier in a previous clinical trial (NCT00434512). Binding responses of serum antibodies targeting a panel of envelope glycoproteins, including gp120, gp140 and V1V2-scaffold antigens and representative of the antigenic diversity of HIV-1, were measured by binding antibody multiplex assay (BAMA). The gp120-specific CD4+/CD8+ T-cell responses were assessed by intracellular cytokine staining assay. Results At Year 14, positive IgG binding antibody responses were detected in 15 out of the 16 antigens from the BAMA V1V2 breadth panel, with positive response rates ranging from 7.1% to 60.7%. The highest response rates were observed for clade B strain V1V2 antigens, with some level of binding antibodies against clade C strains. Anti-V1V2 IgG3 response magnitude breadth, which correlated with decreased risk of infection in a previous efficacy trial, was of limited amplitude. Response rates to the antigens from the gp120 and gp140 breadth panels ranged from 7.7% to 94.1% and from 15.4% to 96.2% at Year 14, respectively. Following stimulation with gp120 peptide pool, highly polyfunctional gp120-specific CD4+ T-cells persisted up to Year 14, with high frequencies of CD40L tumor necrosis factor alpha (TNF-α), CD40L interleukin-2 (IL-2), CD40L TNF-α IL-2 and CD40L interferon gamma (IFN-γ) TNF-α IL-2 CD4+ T-cells, but no CD8+ T-cells detected. Conclusions Persistent antibodies binding to HIV-1 envelope glycoproteins, including the V1V2-scaffold, and gp120-specific cellular immunity were observed in volunteers vaccinated 14 years earlier with the gp120-NefTat/AS01B vaccine candidate.

    更新日期:2020-01-11
  • The Falconi’s needle against anti-vaccination: A minimally invasive tool in the nineteenth century
    Vaccine (IF 3.269) Pub Date : 2020-01-09
    Marcello Trucas

    The history of Giovanni Falconi’s career and his vaccination campaigns is two hundred years old. It is however very relevant today because of the widespread negative social opinion against vaccination at that time, opinions which seem to have re-emerged even in the current century. In his very important role of “Vaccine Conservator” (a sort of national supervisor for the quality of vaccinations), he clashed with the prejudice of the people and with the anti-scientific attitudes of some of his illustrious colleagues. He investigated how to simplify the procedure with a smallpox needle that became known as “Falconi’s Needle” or “Falconian Needle”. Falconi also made several experiments on smallpox vaccine preparation and was a supporter of the use of “animal” and “humanized” formulas despite the prejudice regarding the latter. Due to his profound anatomical knowledge and the strength of mind that characterized him, he was able to follow evidence-based scientific principles in his methods. Thanks to this he managed to convince people not to oppose vaccinations. He also succeeded in bringing the number of vaccinated people to exceed the number of newborns, a great achievement that led to remarkable progress in Italy and the rescue of thousands of lives throughout Europe. Unfortunately, it was not possible to find a copy of this instrument, which required the author to have the needle reconstructed.

    更新日期:2020-01-11
  • Vaccine efficacy of recombinant BmVDAC on Rhipicephalus microplus fed on Babesia bigemina-infected and uninfected cattle
    Vaccine (IF 3.269) Pub Date : 2020-01-09
    Reyna Ortega-Sánchez; Minerva Camacho-Nuez; Jacqueline Elizabeth Castañeda-Ortíz; Máximo Berto Martínez-Benítez; Diego Josimar Hernández-Silva; Gabriela Aguilar-Tipacamú; Juan Mosqueda
    更新日期:2020-01-11
  • Statistical modeling alongside observational data predicts long-term immunogenicity of one dose and two doses of pediatric hepatitis A vaccine in the Mendoza province of Argentina
    Vaccine (IF 3.269) Pub Date : 2020-01-09
    C. Espul; H. Cuello; I. Lo Castro; C. Bravo; Y. Thollot; J. Voznica; C. Vigne; L. Coudeville

    Background Follow-up for anti-hepatitis A (HA) antibody persistence up to 10 years was conducted after implementation of universal vaccination against HA virus (HAV) in Mendoza, Argentina. Based on these data, statistical modeling was used to predict the antibody persistence to 30 years. Methods A non-interventional study evaluated long-term immunogenicity (geometric mean concentrations [GMCs] and seroprotection rate) following routine vaccination with 1 dose (Group 1: N = 436) or 2 doses (Group 2: N = 108) of HA vaccine. Associated statistical modeling based on a Bayesian approach of mixed effects models on log transformed titers evaluated three models (linear, piecewise linear, and exponential decay, with and without a natural boosting effect). Results From the initial cohort, 9 participants (Group 1) and 1 participant (Group 2) showed antibody titers below the seroprotective threshold and received a booster. At Year 10, 190 (Group 1) and 51 (Group 2) participants remained in the study without a booster dose and all were seroprotected. Regarding statistical modeling, the piecewise linear model showed the best fit and demonstrated high and similar seroprotection for each schedule up to 30 years (89% [1-dose schedule], 85% [2-dose schedule]). The 2-dose schedule showed higher GMC (95% CI) than the 1-dose schedule (Year 10: 352 [271–456] versus 78 [69.8–87.6] mIU/mL) and Year 30 (predicted) (37 [13–97] versus 19 [11–34] mIU/mL). Natural boosting had little impact on predicted seroprotection rates at 30 years for the 1-dose schedule (89% [0.8–0.96] and 84% [0.73–0.94] with and without a natural booster, respectively). Conclusions Long-term persistence of anti-HAV antibodies was observed up to 10 years with 1-dose and 2–dose vaccine schedules, supporting booster flexibility. Statistical modeling predicted good persistence of seroprotection for each schedule up to 30 years. Natural boosting had a limited impact on seroprotection rate predictions, enabling extrapolation of these results to non-endemic settings for traveler vaccination.

    更新日期:2020-01-09
  • Immunogenicity of imported foot-and-mouth vaccines in different species in Mongolia
    Vaccine (IF 3.269) Pub Date : 2020-01-09
    Gerelmaa Ulziibat; Odonchimeg Maygmarsuren; Bodisaikhan Khishgee; Ganzorig Basan; Batkhuyag Sandag; Sodnomdarjaa Ruuragc; Georgina Limon; Ginette Wilsden; Clare Browning; Donald P. King; Anna B. Ludi; Nicholas A. Lyons

    Foot-and-mouth disease (FMD) is a high impact viral disease of livestock for which vaccines are extensively used in control. Mongolia has regular incursions of FMD virus that are typically limited to the eastern region although large epidemics are occasionally reported in the normally disease-free western areas. Vaccines are imported and form an important component of the control strategy. In 2015, post-vaccination monitoring guidelines were published by the FAO-OIE recommending approaches for assessing the appropriateness of imported vaccines including small-scale immunogenicity studies. This study used these recommended approaches to guide the use of vaccine adjuvant type and the need for a one or two dose primary course in the national control programme considering cattle, sheep and Bactrian camels and also whether these vaccines were appropriate for the FMD virus lineages considered high risk to Mongolia (A/ASIA/Sea-97; O/SEA/Mya-98; O/ME-SA/PanAsia; O/ME-SA/Ind-2001). The results of these immunogenicity studies indicated that in cattle and sheep, oil-adjuvanted vaccines led to higher and more persistent neutralisation titres that were satisfactory against the target lineages if a two-dose primary course was utilised. In contrast, aqueous-adjuvanted vaccines were associated with lower titres that likely required a booster after 3 months. Levels of antibodies in Bactrian camels were significantly lower although it is unknown how these may correlate with protection under experimental or field exposure conditions. The results of this study have implications for vaccine policy in Mongolia and suggest further studies on the role of Bactrian camels in the epidemiology of FMD are necessary to indicate if further research on FMD vaccines are needed in this species.

    更新日期:2020-01-09
  • Beliefs in vaccine as causes of autism among SPARK cohort caregivers
    Vaccine (IF 3.269) Pub Date : 2020-01-08
    Eric Fombonne; Robin P. Goin-Kochel; Brian J. O'Roak

    Background Fear of autism has led to a decline in childhood-immunization uptake and to a resurgence of preventable infectious diseases. Identifying characteristics of parents who believe in a causal role of vaccines for autism spectrum disorder (ASD) in their child may help targeting educational activities and improve adherence to the immunization schedule. Objectives To compare caregivers of children with ASD who agree or disagree that vaccines play an etiological role in autism for 1) socio-demographics characteristics and 2) developmental and clinical profiles of their children. Methods Data from 16,525 participants with ASD under age 18 were obtained from SPARK, a national research cohort started in 2016. Caregivers completed questionnaires at registration that included questions on beliefs about the etiologic role of childhood immunizations and other factors in ASD. Data were available about family socio-demographic characteristics, first symptoms of autism, developmental regression, co-occurring psychiatric disorders, seizures, and current levels of functioning. Results Participants with ASD were 80.4% male with a mean age of 8.1 years (SD = 4.1). Overall, 16.5% of caregivers endorsed immunizations as perceived causes of autism. Compared to caregivers who disagreed with vaccines as a cause for ASD, those who believed in vaccine causation came disproportionately from ethnic minority, less educated, and less wealthy backgrounds. More often their children had experienced developmental regression involving language and other skills, were diagnosed earlier, had lost skills during the second year of life, and had worse language, adaptive, and cognitive outcomes. Conclusion One in six caregivers who participate in a national research cohort believe that child immunizations could be a cause of autism in their child. Parent social background (non-White, less educated) and child developmental features (regression in second year, poorer language skills, and worse adaptive outcomes) index caregivers who are more likely to harbor these beliefs and could benefit from targeted educational activities.

    更新日期:2020-01-08
  • Modification of neutralizing epitopes of hemagglutinin for the development of broadly protective H9N2 vaccine
    Vaccine (IF 3.269) Pub Date : 2020-01-08
    Zhong Wee Poh; Zhenzhang Wang; Subaschandrabose Rajesh Kumar; Hui Yee Yong; Mookkan Prabakaran

    The H9N2 avian influenza viruses cause significant economic losses in poultry worldwide and could potentially cause human pandemic. Currently, the available vaccines have limited efficacy due to antigenic drift of H9N2. To improve vaccine efficacy, we developed monovalent vaccine strain via the modification of neutralizing epitopes on hemagglutinin (HA) to broaden the protection against H9N2 viruses. In this study, single and multiple mutation were introduced to amino acid at position 148, 150 (site I) and 183, 186, 188 (site II) on the full-length HA gene of H9N2 strain (A/Hong Kong/33982/2009). These mutant HA constructs were displayed on the baculovirus surface (BacH9), and evaluated for their cross-protective efficacy against H9N2 viruses in a mouse model. Our findings indicate that mice immunized with multiple BacH9 mutant constructs (148–150 183 and 186) induced cross-protective immunity against circulating H9N2 in the viral challenge study and prove to be a promising vaccine candidate for H9N2.

    更新日期:2020-01-08
  • A cost-effectiveness analysis of traditional and geographic information system-supported microplanning approaches for routine immunization program management in northern Nigeria
    Vaccine (IF 3.269) Pub Date : 2020-01-08
    Disha Ali; Ann Levin; Masduq Abdulkarim; Usman Tijjani; Bakoji Ahmed; Faruk Namalam; Femi Oyewole; Leanne Dougherty

    Effective RI microplanning requires accurate population estimates and maps showing health facilities and locations of villages and target populations. Traditional microplanning relies on census figures to project target populations and on community estimates of distances, while GIS microplanning uses satellite imagery to estimate target populations and spatial analyses to estimate distances. This paper estimates the cost-effectiveness of geographical information systems (GIS)-based microplanning for routine immunization (RI) programming in two states in northern Nigeria. For our cost-effectiveness analysis, we captured the cost of all inputs for both approaches to capture the incremental cost of GIS over traditional microplanning and present the incremental cost-effectiveness ratios for each vaccine-preventable illness, death, and disability-adjusted life year (DALY) averted. We considered two scenarios for estimating vaccine requirements for each microplanning approach, one based on administrative vaccination coverage rates and one based on National Nutrition and Health Survey rates. With the administrative rates, GIS microplanning projected approximately 194,000 and 157,000 more required vaccinations than traditional microplanning in Bauchi and Sokoto States; with the survey rates, the additional number of vaccinations required was nearly 113,000 in Bauchi and about 47,000 in Sokoto. For each state under each scenario, we present numbers of and costs per measles and pertussis cases, deaths, and DALYs averted by the additional vaccinations, as well as annual costs. As expected, GIS-based microplanning incurs higher costs than traditional microplanning, due mainly to the additional vaccinations required for populations previously unreached. Our estimates of cost per DALY averted suggest, however, that GIS microplanning is more cost-effective than traditional microplanning in both states under both coverage scenarios and that the higher costs incurred by GIS microplanning are worth adopting.

    更新日期:2020-01-08
  • Resilience of HPV vaccine uptake in Denmark: Decline and recovery
    Vaccine (IF 3.269) Pub Date : 2020-01-07
    Peter R. Hansen; Matthias Schmidtblaicher; Noel T. Brewer

    Background Immunization programs’ resilience to shocks is central to their success, but little empirical evidence documents resilience in action. We sought to characterize the decline of HPV vaccination in Denmark after negative media coverage and recovery during a national information campaign. Methods We conducted a population-based retrospective cohort study of all girls born in Denmark from 1997 to 2006 (N = 328,779), aged 12–15. The outcome measure was HPV vaccine uptake (first dose), as reported to the Danish national health registry from 2009 to 2019, when HPV vaccine was freely available to girls in primary care clinics in Denmark. Events that created 4 natural time periods for study were HPV vaccine reaching the uptake of other vaccines in the national program (2009), some negative media coverage of HPV vaccination (2013), extensive negative media coverage (2015), and a national information campaign about the vaccine’s safety and effectiveness (2017–2019). Results In the period with some negative media coverage, HPV vaccine uptake fell to 83.6% (95% CI:78.0%–89.7%) of baseline uptake. In the period with extensive negative media coverage, uptake fell even further to 49.6% (95% CI:44.5%–55.2%) of baseline uptake. After the information campaign, HPV vaccine uptake recovered to its baseline level (109.2%, 95% CI:90.1%–132.4%) due in part to catch-up doses. Despite the recovery, an estimated 26,000 fewer girls initiated the vaccine than if uptake had not declined. Conclusions The experience in Denmark offers one of the first opportunities to document how a nation grappled with negative media coverage of HPV vaccination and the steadying impact of action by national authorities.

    更新日期:2020-01-07
  • A systematic review and meta-analysis of the effectiveness of LAIV4 and IIV in children aged 6 months to 17 years during the 2016–2017 season
    Vaccine (IF 3.269) Pub Date : 2020-01-06
    Raburn M. Mallory; Allyn Bandell; Christopher S. Ambrose; Jing Yu

    As the real-world effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) and inactivated influenza vaccine (IIV) has varied in recent seasons, a systematic review and meta-analysis was conducted to more precisely estimate effectiveness in the 2016–2017 season. Relevant studies were identified from a systematic review of published literature and personal communication with study investigators. Five studies conducted in Canada, Finland, Germany, the United Kingdom, and the United States were identified for inclusion. Data were analyzed using a random effects model, with heterogeneity testing and a sensitivity analysis restricted to test-negative case–control studies. Consolidated vaccine effectiveness estimates against all strains were 69% (95% CI: 46 to 82) for LAIV4 and 47% (95% CI: 29 to 61) for IIV. Heterogeneity testing was not statistically significant, indicating consistency of individual study results. In conclusion, LAIV4 and IIV showed moderate and comparable effectiveness against influenza in children during the 2016–2017 influenza season.

    更新日期:2020-01-06
  • Enhancing the immunogenicity of a DNA vaccine against Streptococcus mutans by attenuating the inhibition of endogenous miR-9
    Vaccine (IF 3.269) Pub Date : 2020-01-06
    Rong Jia; Lingyan Yan; Jihua Guo

    DNA vaccine provides a promising method for preventing and treating diseases. However, the low immunogenicity restricts its application. New approaches are urgent to be explored to enhance the immune response of DNA vaccine. MicroRNAs are endogenous, small non-coding RNAs which play parts in gene expression inhibition. In this study, microRNA-9 (miR-9) was found to inhibit the expression of the GLU-A-P antigen protein encoded by the anti-caries DNA vaccine. Mutation of miR-9 binding sites in the gene fragment encoding GLU-A-P antigen protein significantly increased the expression of antigen protein. Moreover, miR-9 sponge can improve the expression of the GLU-A-P antigen protein. The co-immunization with miR-9 sponge and anti-caries DNA vaccine significantly enhanced the specific immune response in vivo. In conclusion, attenuating the inhibition of endogenous miR-9 enhanced the antigen expression and immunogenicity of the anti-caries DNA vaccine.

    更新日期:2020-01-06
  • The impact of HPV multi-cohort vaccination: Real-world evidence of faster control of HPV-related morbidity
    Vaccine (IF 3.269) Pub Date : 2020-01-06
    Madleen Orumaa; Susanne K. Kjaer; Christian Dehlendorff; Christian Munk; Anne Olaug Olsen; Bo T. Hansen; Suzanne Campbell; Mari Nygård

    Background In 2009, both Norway and Denmark initiated routine quadrivalent human papillomavirus vaccination (qHPV) for 12-year-old girls; however, Denmark also introduced free-of-charge multi-cohort vaccination for older age groups in 2008. We aim to describe trends in genital warts (GWs) incidence rates (IRs) among men and women and qHPV vaccine coverage among women in Norway and Denmark in 2006–2015. Methods We linked multiple national health registries in Norway and Denmark via national personal identifiers to access data on GWs incidence and qHPV vaccination among women and men aged 12–35 years residing in Norway and Denmark in 2006–2015. We calculated age-specific and age-standardized GWs IRs, GWs IR trends before (2006–2009) and after (2009–2015) the implementation of qHPV vaccination, and qHPV vaccine coverage among women. Results In Norway and Denmark together, there were more than 200,000 cases of incident GWs and over 710,000 girls got at least one dose of qHPV vaccine during the study period. The total qHPV coverage in Norway and Denmark in 2015 was among women aged 12–35 years 24% and 70%, respectively. GWs IRs in Norway and Denmark decreased annually in 2009–2015 among women by 4.8% (95% confidence interval: 4.3 to 5.3) and 18.0% (95%CI: 17.5 to 18.6), respectively, and among men 1.9% (95%CI: 1.4 to 2.4) and 10.7% (95%CI: 10.3 to 11.2), respectively. In Denmark, GWs IRs decreased rapidly among both sexes and all age groups after qHPV vaccination, while Norway showed only a modest decrease. Conclusion Rapid decline in HPV-related morbidity is feasible with high coverage of multi-cohort vaccination. However, the decision to vaccinate a single cohort of 12-years-old girls only will postpone HPV-related disease control by at least a decade. Thus countries planning HPV vaccination programs should also initiate multi-cohort vaccination for faster disease control.

    更新日期:2020-01-06
  • Long-term immunogenicity after yellow fever vaccination in immunosuppressed and healthy individuals
    Vaccine (IF 3.269) Pub Date : 2020-01-05
    J. Burkhard; A. Ciurea; C. Gabay; P. Hasler; R. Müller; M. Niedrig; J. Fehr; P. Villiger; L.G. Visser; A.W. de Visser; U.A. Walker; C. Hatz; S. Bühler

    Background The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy. Methods Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA. Results A median time interval of 21.1 years (interquartile range 14.4–31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown). Conclusion The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.

    更新日期:2020-01-06
  • Application of advanced quantification techniques in nanoparticle-based vaccine development with the Sf9 cell baculovirus expression system
    Vaccine (IF 3.269) Pub Date : 2020-01-05
    Eduard Puente-Massaguer; Martí Lecina; Francesc Gòdia

    Nanoparticles generated by recombinant technologies are receiving increased interest in several applications, particularly the use of virus like particles (VLPs) for the generation of safer vaccines. The characterization and quantification of these nanoparticles with complex structures is very relevant for a better comprehension of the production systems and should circumvent the limitations of the most conventional quantification techniques often used. Here, we applied confocal microscopy, flow virometry and nanoparticle tracking analysis (NTA) to assess the production process of Gag virus-like particles (VLPs) in the Sf9 cell/baculovirus expression vector system (BEVS). These novel techniques were implemented in an optimization workflow based on Design of Experiments (DoE) and desirability functions to determine the best production conditions. A higher level of sensitivity was observed for NTA and confocal microscopy but flow virometry proved to be more accurate. Interestingly, extracellular vesicles were detected as an important source of contamination of this system. The synergistic interplay of viable cell concentration at infection (CCI), multiplicity of infection (MOI) and time of harvest (TOH) was assessed on five objective responses: VLP assembly, baculovirus infection, VLP production, cell viability and VLP productivity. Two global optimal conditions were defined, one targeting the maximal yield of VLPs and the other providing a balance between production and assembled VLPs. In both cases, a low MOI proved to be the best condition to achieve the highest VLP production and productivity yields. Cryo-EM analysis of nanoparticles produced in these conditions showed the typical size and morphology of HIV-1 VLPs. This study presents an integrative approach based on the combination of DoE and direct nanoparticle quantification techniques to comprehensively optimize the production of VLPs and other viral-based biotherapeutics.

    更新日期:2020-01-06
  • Simultaneous cognate epitope recognition by bovine CD4 and CD8 T cells is essential for primary expansion of antigen-specific cytotoxic T-cells following ex vivo stimulation with a candidate Mycobacterium avium subsp. paratuberculosis peptide vaccine
    Vaccine (IF 3.269) Pub Date : 2020-01-03
    Gaber S. Abdellrazeq; Lindsay M. Fry; Mahmoud M. Elnaggar; John P. Bannantine; David A. Schneider; William M. Chamberlin; Asmaa H.A. Mahmoud; Kun-Taek Park; Victoria Hulubei; William C. Davis

    Studies in cattle show CD8 cytotoxic T cells (CTL), with the ability to kill intracellular bacteria, develop following stimulation of monocyte-depleted peripheral blood mononuclear cells (mdPBMC) with antigen presenting cells (APC, i.e. conventional dendritic cells [cDC] and monocyte-derived DC [MoDC]) pulsed with MMP, a membrane protein from Mycobacterium avium subsp. paratuberculosis (Map) encoded by MAP2121c. CTL activity was diminished if CD4 T cells were depleted from mdPBMC before antigen (Ag) presentation by APC, suggesting simultaneous cognate recognition of MMP epitopes presented by MHC I and MHC II molecules to CD4 and CD8 T cells is essential for development of CTL activity. To explore this possibility, studies were conducted with mdPBMC cultures in the presence of monoclonal antibodies (mAbs) specific for MHC class I and MHC class II molecules. The CTL response of mdPBMC to MMP-pulsed APC was completely blocked in the presence of mAbs to both MHC I and II molecules and also blocked in the presence of mAbs to either MHC I or MHC II alone. The results demonstrate simultaneous cognate recognition of Ag by CD4 and CD8 T cells is essential for delivery of CD4 T cell help to CD8 T cells to elicit development of CTL.

    更新日期:2020-01-04
  • Evaluation of the protective efficacy of recombinant protective antigen vaccine (GC1109)-immunized human sera using passive immunization in a mouse model
    Vaccine (IF 3.269) Pub Date : 2020-01-03
    Su Kyoung Jo; Bo-Eun Ahn; Eun Hye Choi; Ji Eun Kang; Hyonggin An; Myoung-don Oh; Gi-eun Rhie

    The protective efficacy of human sera from vaccinated individuals with a new recombinant protective antigen anthrax vaccine (GC1109) against lethal spore challenge was evaluated in a mouse model. Eighteen human sera were selected from the vaccinated individuals based on their toxin neutralizing assay (TNA) titer (ED50 of 55 to 668). The selected sera were diluted and passively transferred to A/J mice and the mice were subsequently challenged with 100 × LD50 of Bacillus anthracis Sterne spores. The correlation between the survival rate of passively immunized mice and the TNA ED50 of transferred sera was presented (r = 0.873, P-value < 0.001). The estimated TNA titer for 50% survival rate against lethal challenge was 197 (95% confidence interval of 149 and 260). The result suggest that GC1109 is protective against exposure to B. anthracis and the TNA titer of vaccinated serum can be an indicator for protective efficacy.

    更新日期:2020-01-04
  • Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals
    Vaccine (IF 3.269) Pub Date : 2020-01-03
    Sarah Sterrett; Binghao J. Peng; Robert L. Burton; David C. LaFon; Andrew O. Westfall; Suddham Singh; Michael Pride; Annaliesa S. Anderson; Gregory C. Ippolito; Harry W Schroeder; Moon H. Nahm; A. Krishna Prasad; Paul Goepfert; Anju Bansal

    Background PCV13 (conjugated polysaccharide) and PPSV23 (polysaccharide only) are two licensed vaccines targeting S. pneumoniae. The role of CD4 T-cell responses in pneumococcal vaccines among healthy participants and their impact on antibodies is not yet known. Methods Ten adults (5 old and 5 young) received PCV13 (prime) and a year later PPSV23 (boost). Blood samples were collected prior to and multiple time points after vaccination. CD4 T cells responding to CRM197, polysaccharide (PS), CRM197 conjugated polysaccharide (CPS), PCV13 and PPSV23 vaccines were measured by flow cytometry. Serum antibodies were analyzed via multiplex opsonophagocytosis (MOPA) and pneumococcal IgG assays. Results Vaccine-specific CD4 T cells were induced in all ten vaccinees post PCV13. Older vaccinees mounted higher peak responses and those specific for PCV13 and conjugated PS-1 were more polyfunctional compared to the younger group. Vaccine-elicited peripheral T follicular helper (Tfh) cells were only detected in the younger group who also exhibited a higher fold change in OPA titers post both vaccines. Importantly, Tfh cells following PCV13 correlated only with PCV13 serotype specific OPA titers after PPSV23 vaccination. Conclusions These findings demonstrate age related differences in immune response and the potential importance of Tfh in modulating functional antibody responses following pneumococcal vaccination.

    更新日期:2020-01-04
  • Evidence of vaccinia dissemination despite lack of major reaction following smallpox vaccination
    Vaccine (IF 3.269) Pub Date : 2019-12-31
    Wilfred P. Delacruz; Michael R. Savona; Jennifer A. Thornton; Patrick J. Danaher

    Following vaccinia vaccination, vesicle formation at the site occurs in 95% of primary vaccinees and is thought to indicate virus replication and vaccine efficacy. Little is known about virus replication and immune response in those who do not develop a vesicle. We used PCR to detect vaccinia in various sites following receipt of the smallpox vaccine in those with and without vesicle formation. Among 80 participants, 74 developed and 6 failed to develop a vesicle. Vaccinia DNA was detected in the blood, in the oropharynx, on the dressing, and on the hands of 5%, 11%, 4%, and 0% of those with vesicle formation and of 33%, 17%, 0%, and 17% of those without vesicle formation, respectively (p > 0.05 for each site). The detection of systemic vaccinia DNA in vaccinees without vesicle formation challenges the current understanding that lack of vesicle formation indicates lack of virus replication, the prerequisite to immune response.

    更新日期:2019-12-31
  • A phase 1 antigen dose escalation trial to evaluate safety, tolerability and immunogenicity of the leprosy vaccine candidate LepVax (LEP-F1 + GLA–SE) in healthy adults
    Vaccine (IF 3.269) Pub Date : 2019-12-30
    Malcolm S. Duthie; Aude Frevol; Tracey Day; Rhea N. Coler; Julie Vergara; Tom Rolf; Zachary K. Sagawa; Anna Marie Beckmann; Corey Casper; Steven G. Reed

    Healthy United States-based adult volunteers with no history of travel to leprosy-endemic countries were enrolled for the first-in-human evaluation of LepVax (LEP-F1 + GLA-SE). In total 24 volunteers participated in an open-label clinical trial, with 21 receiving three injections of LepVax consisting of either 2 µg or 10 µg recombinant polyprotein LEP-F1 mixed with 5 µg of the GLA-SE adjuvant formulation. LepVax doses were provided by intramuscular injection on Days 0, 28, and 56, and safety was evaluated for one year following the final injection. LepVax was safe and well tolerated at both antigen doses. Immunological analyses indicated that similar LEP-F1-specific antibody and Th1 cytokine secretion (IFN-γ, IL-2, TNF) were induced by each of the antigen doses evaluated within LepVax. This clinical trial of the first defined vaccine candidate for leprosy demonstrates that LepVax is safe and immunogenic in healthy subjects and supports its advancement to testing in leprosy-endemic regions.

    更新日期:2019-12-31
  • The interference effect of maternally-derived antibodies on the serological performance of pigs immunized with a foot-and-mouth disease oil emulsion vaccine
    Vaccine (IF 3.269) Pub Date : 2019-12-28
    Jaejo Kim; Taeseong Kim; Jang-Kwan Hong; Hyang-Sim Lee; Kwang-Nyeong Lee; Hye Jun Jo; Jieun Choi; Jida Choi; Seung Heon Lee; Myoung-Heon Lee; Byounghan Kim; Jong-Hyeon Park

    To control foot-and-mouth disease (FMD) outbreaks that originated in Jincheon County in South Korea between 2014 and 2015, several commercial vaccines were studied for their efficacy and serological performance in the field. In this study, the efficacy of the O SKR 7/10 vaccine was evaluated by challenge with the FMD virus (FMDV) O/Jincheon/SKR/2014 (O Jincheon), which has the same O/SEA/Mya-98 lineage as the O/SKR/7/10 strain that was isolated in 2010 in South Korea, in FMD-seronegative pigs. Full protection against the O Jincheon virus was demonstrated as early as 14 days postvaccination, which was explained by the strong serological relationship (r1 value: ≥ 0.92) between the O Jincheon and O SKR 2010 viruses. However, in the field trial, no satisfactory serological elevations against FMDV were observed, even in the double-vaccinated groups. Therefore, it can be concluded that the O SKR 7/10 vaccine may need to be improved to overcome the interference effects from the high levels of maternally-derived antibodies generated due to the mandatory nationwide vaccination of sows in South Korea.

    更新日期:2019-12-29
  • Effectiveness of enterovirus A71 vaccine in severe hand, foot, and mouth disease cases in Guangxi, China
    Vaccine (IF 3.269) Pub Date : 2019-12-28
    Lina Jiang; Jing Wang; Chao Zhang; Weitao He; Jianjun Mo; Jun Zeng; Minmei Chen; Yi Tan; Chuanyi Ning

    Background Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) is a major public health issue in China that poses severe risks to children’s health, especially those under the age of 3. Since 2016, EV71 vaccines developed by three Chinese manufacturers have been approved for use, and clinical trials of these vaccines have demonstrated protection against EV-A71 infection. However, few studies have assessed the effectiveness of these vaccines in real-world settings. Methods A test-negative design case-control study was used to estimate vaccine effectiveness (VE) in cases of severe HFMD. We obtained information including EV-A71 vaccination status from the Local Center for Disease Control and Prevention (CDC) on all severe HFMD cases under 12 years in age in Guangxi, China, from Jan. 1, 2017, to Dec. 31, 2018. Enterovirus infection was laboratory confirmed by local CDCs. Individuals with a positive EV-A71 nucleic acid test result were assigned to the case group, and those with negative EV-A71 nucleic acid test results were assigned to the control group. We estimated VE using logistic regression. Results A total of 2779 severe HFMD cases were enrolled in the study; 838 children were EV-A71 positive cases, and 1941 children were EV-A71 negative controls. The proportion of EV-A71 positive cases aged 6–36 months was lower than that for EV-A71 negative controls. EV-A71 infection was associated with an increased risk of mortality (aOR, 8.8; 95% CI, 1.3–61.6). The adjusted VE was 81.4% and 88.3% for one dose and two doses, respectively. Conclusion Our findings suggest that the rate of EV-A71 has fallen among severe HFMD cases in Guangxi and that the risk for EV-A71 infection in 6–36-month-old children has been reduced by use of the vaccine. Inactivated vaccines performed well in severe HFMD cases in a real-world setting.

    更新日期:2019-12-29
  • Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study
    Vaccine (IF 3.269) Pub Date : 2019-12-27
    Karen A. McIlhone; Emma J. Best; Helen Petousis-Harris; Anna S. Howe

    Background Rotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016. Methods A national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area. Results Significant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847). Conclusions In New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.

    更新日期:2019-12-29
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