Elsevier

Journal of Clinical Virology

Volume 117, August 2019, Pages 68-72
Journal of Clinical Virology

Characterization of antibody response in patients with acute and chronic chikungunya virus disease

https://doi.org/10.1016/j.jcv.2019.06.001Get rights and content

Highlights

  • We found no difference between homologous and heterologous cross-neutralization of chikungunya virus.

  • Complement significantly increased virus neutralization titers when high viral load was used.

  • Patients with acute chikungunya disease had a significantly higher antibody avidity index compared to those with chronic disease.

Abstract

Background

Chikungunya virus (CHIKV) is a re-emerging arbovirus capable of causing chronic arthralgia, which can last for months to years. Although neutralizing antibodies have been shown to be important for viral clearance, is it not clear whether the quantitative and qualitative nature of antibodies play a role in progression to chronic disease.

Objectives

To characterize and compare the antibody responses in acute and chronic patients in a prospective observational CHIKV study in Curaçao during the 2014-2015 outbreak.

Study design

We performed virus neutralization tests and ELISA on plasma samples collected from a prospective observational chikungunya study in Curaçao to compare the complement-dependent and –independent neutralization capacity, as well as the antibody avidity index of acute and chronic patients.

Results

We found that there was no significant difference in the virus neutralization titers between patients with acute and chronic chikungunya infection. Furthermore, we found that complement increased the neutralization capacity when large amounts of virus was used. Moreover, we found that patients with acute chikungunya disease had a significantly higher antibody avidity index compared to those with chronic disease.

Conclusions

This study suggests that virus neutralization titers in late convalescent sera do not play a role in chronic chikungunya. However, the median antibody avidity was lower in these patients and may therefore suggest a role for antibody avidity in the development of chronic disease.

Section snippets

Background

Chikungunya virus (CHIKV) belongs to the genus alphavirus of the Togaviridae family. Following acute infection, 20–50% of patients develop chronic symptoms lasting between weeks to years [1,2]. Both innate and adaptive immunity have been proposed to play a role in the development of chronic disease, but the complete mechanisms are still unclear [3]. Antibodies to CHIKV have been shown to be important for viral clearance and mediate protection against re-infection [4,5]. Although neutralizing

Objectives

To characterize the antibody response in plasma of patients with acute and chronic CHIKV disease.

Patients

This study was a prospective observational study conducted in Curaçao, which is a continuation from a previous report [14]. The selection of patients was based on the availability of clinical symptoms and plasma sample during follow-up. Patients that still experienced chronic symptoms after 3 months (arthralgia and/or myalgia) were defined as “chronic disease” while patients with no symptoms were defined as having had an “acute disease”. IgM/IgG ELISA (IBL, Germany) and qRT-PCR were also

Cohort description

Fifty-two patients were diagnosed with chronic disease and 38 patients with acute disease. The median follow-up time for the sample collection was 12 months (range 3–14 months) for both groups. All follow-up samples were negative for CHIKV RNA and positive for anti−CHIKV IgGs. Three patients showed measurable levels of anti−CHIKV IgM in the follow-up samples, which were taken 12 months (2 patients) and 6 months (1 patient) post-infection. Two patients belonged to the acute group while one

Discussion

This manuscript describes several properties of the antibody response in a cohort of CHIKV patients. Firstly, our data revealed that NABs produced against one genotype of CHIKV are cross-reactive against another genotype. This result is in agreement with the other studies showing complete cross-neutralization [22,23]. The high percentage of amino acid similarity among all CHIKV strains [24] together with minimal differences in vaccine-NAB responses observed among genotypes [25] indicate that

Conclusions

Our results indicate that VNT50 was not different between patients with acute and chronic chikungunya. However, complement increased the neutralization capacity against CHIKV when high amount of virus was used. Finally, the average AI against E1 and E2 glycoproteins was higher in the acute compared to chronic group.

Credit author statement

FA and BEEM conceptualized and designed the study. FA, SML and SF performed the experiments. RW contributed in the sample collections and reagents. FA, SML, SF, RW, ADMEO and BEEM all contributed in the planning of the manuscript, data analysis and interpretion, and critical review and approval of the manuscript.

Ethical approval

Ethical clearance for this study was obtained from the Medical Ethics Committee of Curaçao (ref. no. 2014-003). Written informed consent was obtained from enrolled patients.

Funding

FA was supported by the Directorate of Higher Education (DIKTI) PhD grant of the Ministry of Research, Technology and Higher Education of the Republic of Indonesia. The funders had no role in study design, data collection and analysis, preparation of the manuscript, and decision to publish.

Acknowledgement

The authors would like to thank the physicians, the lab technicians and the patients in Curaçao for their help and support in this study.

References (36)

  • X.J. Da Costa et al.

    Humoral response to herpes simplex virus is complement-dependent

    Proc. Natl. Acad. Sci. U. S. A.

    (1999)
  • E. Mehlhop et al.

    Complement activation is required for induction of a protective antibody response against West Nile virus infection

    J. Virol.

    (2005)
  • R.L. Hirsch et al.

    The role of complement in viral infections. II. the clearance of Sindbis virus from the bloodstream and central nervous system of mice depleted of complement

    J. Infect. Dis.

    (1980)
  • R.L. Hirsch et al.

    The role of complement in viral infections. III. Activation of the classical and alternative complement pathways by Sindbis virus

    J. Immunol.

    (1980)
  • R.L. Hirsch et al.

    Role of complement in viral infections: participation of terminal complement components (C5 to C9) in recovery of mice from Sindbis virus infection

    Infect. Immun.

    (1980)
  • T.E. Morrison et al.

    Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease

    J. Virol.

    (2007)
  • P. Laurent et al.

    Development of a sensitive real-time reverse transcriptase PCR assay with an internal control to detect and quantify chikungunya virus

    Clin. Chem.

    (2007)
  • P. van den Doel et al.

    Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge

    PLoS Negl. Trop. Dis.

    (2014)
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