ArticlesSafety, immunogenicity, and transplacental antibody transport of conjugated and polysaccharide pneumococcal vaccines administered to pregnant women with HIV: a multicentre randomised controlled trial
Introduction
Pneumococcus has been a leading cause of bacterial pneumonia in pregnant and non-pregnant adults with HIV.1 Even with the widespread use of antiretroviral therapy (ART), the incidence of invasive pneumococcal disease and pneumonia remains higher in people with HIV than in same-age adults without HIV.2 Invasive pneumococcal disease and pneumococcal pneumonia are vaccine-preventable conditions to a large extent.3 There are currently two types of vaccines available against pneumococcus: a polysaccharide vaccine (PPV) that is 23-valent (PPV-23) and two conjugated vaccines (PCVs) that are 10-valent (PCV-10) and 13-valent (PCV-13). The efficacy of PPV-23 in preventing invasive pneumococcal disease and all-cause pneumonia in people with HIV was shown in several non-randomised studies,4 but the only prospective, randomised, placebo-controlled trial showed a decrease in all-cause mortality but not in all-cause pneumonia.5 The efficacy of PCVs was shown both in children and adults with HIV.6, 7 PCV-7 and PCV-9 were shown to be safe and immunogenic in people with HIV.8 However, individuals with lower CD4 cell count or higher concentration of HIV plasma RNA had higher antibody responses to PCV-7 than to PPV-23.8 Pregnancy is associated with immunosuppression, which helps to protect the fetus against allogeneic rejection. However, before this study, there was one report on the immunogenicity of PPV-23 in pregnant women with HIV and no data for PCV-10 and PCV-23.9
Although the administration of pneumococcal vaccines to adults with HIV has been recommended in the USA for over 25 years, a survey of the International Maternal, Pediatric and Adolescent AIDS Clinical Trials clinical sites done before the inception of this study showed that pneumococcal vaccination was generally not given during pregnancy.3 Around 25% of women in the USA are first diagnosed with HIV during pregnancy.10 This finding constitutes a missed opportunity, because bacterial pneumonias are more common in pregnant women than in non-pregnant adults with HIV and are associated with an increased risk of maternal morbidity and mortality and adverse pregnancy outcomes.1 The most common barrier against any vaccine administration during pregnancy is the potential risk of adverse pregnancy outcome perceived by mothers and their health-care providers.11
In addition to maternal protection against infection, vaccination of pregnant women results in transplacental transport of maternal antibodies that might protect infants in the first few months of life. This protection has been clearly shown for influenza and pertussis and has been proposed for other infections, including pneumococcus.12, 13 Although the introduction of PCVs in the childhood schedule of immunisation has generally decreased the incidence of severe pneumococcal disease in children younger than 2 years, infants exposed in utero to HIV still have an increased risk of severe pneumonia and invasive pneumococcal disease irrespective of their HIV infection status.14 Transplacental transport of pathogen-specific maternal antibodies decreases in the context of HIV infection, and this decrease might contribute to the high risk of invasive pneumococcal disease and severe pneumonia in HIV-exposed infants.15 This high risk could potentially be mitigated by increasing maternal anti-pneumococcus antibody concentrations through immunisation.
To address the knowledge gap surrounding anti-pneumococcus immunisation in pregnant women with HIV, we designed a randomised, double-blind, placebo-controlled trial to measure the safety, immunogenicity, and transplacental transport of maternal antibodies in women with HIV who have been vaccinated against pneumococcus during pregnancy. The underlying hypotheses were that PPV-23 and PCV-10 were safe and increased maternal pneumococcal antibodies compared with placebo.
Section snippets
Study design and participants
This multicentre, double-blind, randomised controlled trial was done at eight outpatient clinics of the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Brazil under approval of national and local regulatory review boards. Ethics approval was obtained by the National Research Ethics Commission. All participants gave written informed consent before enrolment. The study planned to enrol pregnant women with HIV at a gestational age between 14 weeks and less than
Results
Between April 1, 2016, and Nov 30, 2017, we enrolled 347 pregnant women with HIV, including 346 who received study treatment (figure 1). The number of study candidates who declined participation was not recorded. Among the 347 participants, 116 were randomised to the PCV-10 group, 115 to the PPV-23 group, and 116 to the placebo group. One participant randomised to the PCV-10 group did not return to clinic to receive the vaccine and was excluded from subsequent analyses. At baseline,
Discussion
To our knowledge, this study was the first randomised, double-blind, placebo-controlled study comparing PCV-10 with PPV-23 and both vaccines with placebo in pregnant women. We showed that PCV-10 and PPV-23 were generally safe and highly immunogenic in pregnant women with HIV. Compared with placebo, both vaccines significantly increased the antibody concentrations against all the vaccine serotypes tested and 65% of the mothers had seroresponse against at least five of seven serotypes common to
Data sharing
Data obtained in this study, including deidentified individual participant data reported in this Article and a data dictionary defining each field in the set, will be made available to other investigators. Data will be made available immediately following publication, with no end date, to researchers who provide a methodologically sound proposal to the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Data will be available at https://dash.nichd.nih.gov/.
Declaration of interests
AW receives grants from the US National Institutes of Health, GlaxoSmithKline, Janssen, and Merck. TF and PM receive grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. SIP receives personal fees from Merck, Sanofi, and Pfizer, and grants from the US National Institutes of Health and Pfizer. DG receives personal fees from Merck and grants from GlaxoSmithKline and Merck. All other authors declare no competing interests.
References (30)
- et al.
Pneumococcal disease prevention among adults: strategies for the use of pneumococcal vaccines
Am J Prev Med
(2015) - et al.
Immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-infected pregnant women and kinetics of passively acquired antibodies in young infants
Vaccine
(2009) - et al.
Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation
Vaccine
(2001) - et al.
Fc characteristics mediate selective placental transfer of IgG in HIV-infected women
Cell
(2019) - et al.
Revaccination with 7-valent pneumococcal conjugate vaccine elicits better serologic response than 23-valent pneumococcal polysaccharide vaccine in HIV-infected adult patients who have undergone primary vaccination with 23-valent pneumococcal polysaccharide vaccine in the era of combination antiretroviral therapy
Vaccine
(2014) - et al.
Immunogenicity and reactogenicity of 23-valent pneumococcal polysaccharide vaccine among pregnant Filipino women and placental transfer of antibodies
Vaccine
(2007) - et al.
Serum, breast milk, and infant antibody after maternal immunisation with pneumococcal vaccine
Lancet
(1995) - et al.
Total and serotype-specific pneumococcal antibody titres in children with normal and abnormal humoral immunity
Vaccine
(2006) - et al.
Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil
Vaccine
(2019) - et al.
HIV-associated maternal mortality—primary causes of death at King Edward VIII Hospital, Durban
S Afr Med J
(2007)
Invasive pneumococcal disease among HIV-positive individuals, 2000–2009
AIDS
A case-control study to investigate serological correlates of clinical failure of 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults
J Infect Dis
Impact of pneumococcal vaccination on the incidence of pneumonia by HIV infection status among patients enrolled in the Veterans Aging Cohort 5-Site Study
Clin Infect Dis
A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults
N Engl J Med
A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection
N Engl J Med
Cited by (8)
Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023
2023, MMWR Recommendations and ReportsImmunogenicity of Conjugated and Polysaccharide Pneumococcal Vaccines Administered during Pregnancy or Postpartum to Women with HIV
2022, Journal of Infectious Diseases