Unique epitopes recognized by antibodies induced in Chikungunya virus-infected non-human primates: implications for the study of immunopathology and vaccine development

PLoS One. 2014 Apr 22;9(4):e95647. doi: 10.1371/journal.pone.0095647. eCollection 2014.

Abstract

Chikungunya virus (CHIKV) is an Alphavirus that causes chronic and incapacitating arthralgia in humans. Although patient cohort studies have shown the production of CHIKV specific antibodies, the fine specificity of the antibody response against CHIKV is not completely defined. The macaque model of CHIKV infection was established due to limitations of clinical specimens. More importantly, its close relation to humans will allow the study of chronic infection and further identify important CHIKV targets. In this study, serum samples from CHIKV-infected macaques collected at different time-points post infection were used to characterize the antibody production pattern and kinetics. Results revealed that anti-CHIKV antibodies were neutralizing and the E2 glycoprotein, Capsid, nsP1, nsP3 and nsP4 proteins were targets of the anti-CHIKV antibody response in macaques. Furthermore, linear B-cell epitopes recognized by these anti-CHIKV antibodies were identified, and mapped to their structural localization. This characterizes the specificity of anti-CHIKV antibody response in macaques and further demonstrates the importance of the different regions in CHIKV-encoded proteins in the adaptive immune response. Information from this study provides critical knowledge that will aid in the understanding of CHIKV infection and immunity, vaccine design, and pre-clinical efficacy studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology*
  • Antibody Specificity / immunology
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Cell Line
  • Chikungunya Fever / immunology*
  • Chikungunya Fever / prevention & control*
  • Chikungunya virus / immunology*
  • Chikungunya virus / metabolism
  • Disease Models, Animal
  • Epitope Mapping
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Models, Molecular
  • Neutralization Tests
  • Primates
  • Protein Binding / immunology
  • Protein Conformation
  • Viral Proteins / immunology
  • Viral Proteins / metabolism
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes
  • Epitopes, B-Lymphocyte
  • Immunoglobulin G
  • Viral Proteins
  • Viral Vaccines

Grants and funding

This work was supported by the Biomedical Research Council (BMRC) and a research grant by the Joint Council Office (JCO), A*STAR. Part of this work was also supported by the European Union project: Integration of Chikungunya RESearch “ICRES” grant number 261202. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.