Analysis of Humoral Immune Responses in Chikungunya Virus (CHIKV)-Infected Patients and Individuals Vaccinated With a Candidate CHIKV Vaccine

J Infect Dis. 2020 Apr 27;221(10):1713-1723. doi: 10.1093/infdis/jiz658.

Abstract

Background: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after 1 week, but chronic arthralgia can persist for years. In this study, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed.

Methods: Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors, and antibody epitope mapping was performed with a peptide array.

Results: The greatest CHIKV neutralization activity was observed 60-92 days after onset of symptoms. The amount of CHIKV-specific antibodies and their binding avidity and cross-reactivity with other alphaviruses increased over time. Chikungunya virus and o'nyong-nyong virus (ONNV) were both neutralized to a similar extent. Linear antibody binding epitopes were mainly found in E2 domain B and the acid-sensitive regions (ASRs). In addition, serum samples from healthy volunteers vaccinated with a measles-vectored chikungunya vaccine candidate, MV-CHIK, were analyzed. Neutralization activity in the samples from the vaccine cohort was 2- to 6-fold lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination only induced cross-neutralization with ONNV, and the E2 ASR1 was the major antibody target.

Conclusions: These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.

Keywords: alphavirus; antibody; chikungunya; neutralization.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood*
  • Antibody Specificity
  • Chikungunya Fever / blood
  • Chikungunya Fever / prevention & control*
  • Chikungunya virus / immunology*
  • Epitope Mapping
  • Gene Expression Regulation, Viral
  • HEK293 Cells
  • Humans
  • Immunity, Humoral*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Protein Conformation
  • Proteome
  • Vaccination
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Proteome
  • Viral Vaccines