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

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe flu-like symptoms. The acute symptoms disappear after one week, but chronic arthralgia can persist for years. Here, humoral immune responses in CHIKV-infected patients and vaccinees were analyzed. Alphavirus neutralization activity was analyzed with pseudotyped lentiviral vectors and antibody epitope mapping was performed with a peptide array. The greatest CHIKV neutralization activity was observed 60–92 days after onset of symptoms. The amount of CHIKV-specific antibodies, their binding avidity, and cross-reactivity with other alphaviruses increased over time. CHIKV 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 lower than in samples from CHIKV-infected patients. In contrast to infection, vaccination induced cross-neutralization with ONNV and the E2 ASR1 was the major antibody target. These data could assist vaccine design and enable the identification of correlates of protection necessary for vaccine efficacy.