Evaluating epitope-specific antibody immunity elicited by chikungunya infection and vaccination Restricted; Files Only
Kapila, Pragati (Spring 2023)
Abstract
Chikungunya virus (CHIKV) is an alphavirus transmitted to human by Aedes mosquitoes and causes symptoms like fever, rash, and joint pain, which may persist from months to years after the initial infection. CHIKV poses as a public health risk to people across tropical and subtropic regions as CHIKV epidemics can overwhelm health systems and burden economies. There are currently no licensed vaccines or approved antivirals against CHIKV. Previous research has established that neutralizing antibodies (NAbs) are an important component of the human immune response to CHIKV and frequently target the E2 glycoprotein on the CHIKV surface. However, current serological measures of immunogenicity of CHIKV vaccines are insufficient. We hypothesize that vaccine candidates eliciting antibodies (Abs) at the same antigenic regions as those of natural CHIKV infection will provide durable immunity. In this paper, a blockage of binding (BOB) assay employing CHIKV-specific neutralizing monoclonal antibodies (NmAbs) was utilized to assess the specificity of Abs elicited by a virus-like particle (VLP) vaccine candidate and a live-attenuated vaccine candidate compared to natural CHIKV infection. BOB activity was measured using one mouse and two human NmAbs. We identified 115 CHIKV IgG positive samples of 296 cross-sectional serum samples obtained from participants residing in a CHIKV-endemic region of Colombia ~4-6 years after CHIKV emerged in the local population. CHIKV-immune sera consistently and strongly competed with the NmAbs tested by BOB. However, a minor portion of participants exhibited strong BOB responses to 1-2 NmAbs and negligible activity to other NmAb(s), suggesting person-to-person variation in immunodominance hierarchies in the Ab response generated by CHIKV infection. The VLP vaccine samples and the live attenuated vaccine samples both demonstrated high consistent BOB activity as well, supporting the hypothesis that similar antigenic regions on the E2 protein were targeted. Finally, BOB activity was positively correlated with NAb titers in all sample sets. Thus, the BOB assays implemented here demonstrated great potential as a robust measure of immunogenicity to guide CHIKV vaccine development.
Table of Contents
Introduction…………………………………………………………………………………….….1
Methods…………………………………………………………………………………….……....2
Results…………………………………………………………………………………….……......5
Discussion….………………………………………………………………………….………......8
References….………………………………………………………………………………….....12
Appendix ….…………………………………………………………………………………......14
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File download under embargo until 19 May 2025 | 2023-05-01 10:34:11 -0400 | File download under embargo until 19 May 2025 |
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