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

Author:

Henss Lisa1,Yue Constanze1,Von Rhein Christine1,Tschismarov Roland2,Lewis-Ximenez Lia Laura3,Dölle Albert4,Baylis Sally A1,Schnierle Barbara S1

Affiliation:

1. Paul-Ehrlich-Institut, Department of Virology, Langen, Germany

2. Themis Bioscience GmbH, Vienna, Austria

3. Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil

4. Independent Researcher, Langen, Germany

Abstract

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.

Funder

German Ministry of Health

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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