Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera.

Chong-Long Chua,Yoke-Fun Chan,I-Ching Sam,Andres Merits

doi:10.1371/journal.pntd.0004960

Chong-Long Chua, Yoke-Fun Chan + Show 2 more

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https://doi.org/10.1371/journal.pntd.0004960

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Abstract

BackgroundChikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood.Methodology/Principal FindingsWe characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008–2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.Conclusion/SignificanceImmune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.

Highlights

Chikungunya virus (CHIKV) is a re-emerging, mosquito-borne arbovirus which has caused unprecedented worldwide epidemics in recent years [1]
We used serum from Malaysian patients infected with CHIKV of either Asian or East/Central/South African (ECSA) genotypes
We identified the key amino acids/epitopes within the E1-E2 surface glycoprotein, and showed that variation of these impacts the efficacy of antiserum in cross-neutralizing different genotypes of CHIKV

Summary

Introduction

Chikungunya virus (CHIKV) is a re-emerging, mosquito-borne arbovirus which has caused unprecedented worldwide epidemics in recent years [1]. There are three major CHIKV genotypes circulating: West African, East/ Central/ South African (ECSA) and Asian [2]. After the global outbreaks of ECSA between 2005 and 2010, the Asian genotype has re-emerged to cause large outbreaks in the Americas and the Pacific islands [3, 4]. Malaysia has experienced CHIKV outbreaks due to two different genotypes, Asian and ECSA. The endemic Asian CHIKV strain was responsible for small, geographically-restricted outbreaks in 1998 and 2006 [5,6,7]. An imported ECSA outbreak was reported in 2006 prior to an explosive nationwide outbreak which affected over 15,000 people across different states in 2008 [8, 9]

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