Differential B Cell Epitope Recognition in Closely Related Arbovirus Infections 2260486

Abstract Introduction Infections caused by related viruses challenge rapid identification, impeding therapeutic decisions. The co-circulation of Zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) in endemic regions complicates viral diagnosis due to shared symptoms and antibody cross-reactivity. The identities of viral epitopes that induce antibodies inform B cell responses during natural infection, which are crucial for understanding viral pathogenesis, vaccine design, and viral diagnosis. Methods A cohort of Colombian patient serum samples collected from ZIKV-endemic and non-endemic areas was used to identify ZIKV epitopes recognized by serum antibodies during early (< 12 weeks post-infection) and late convalescence (>12 weeks). Screening was performed with overlapping peptides spanning the entire ZIKV polyprotein, followed by validation using synthetic linear peptides. Results We identified immunoreactive epitopes that were recognized by serum antibodies from individuals infected (or co-infected) with ZIKV, DENV, or CHIKV at early and later times after infection. A unique subset of peptides (n = 14) was identified to differentiate early from late ZIKV infection and to develop virus-specific diagnostic methods. Conclusion Diverse linear ZIKV epitopes from structural and non-structural proteins that elicited antibodies with unique specificities during natural infection were identified. The differential antibody recognition patterns between early and late convalescence reveal the antibody diversification from the early extrafollicular response to the later germinal center response, providing insight to distinguish early from late convalescence. Comparative analysis of paired sera suggests the dynamic antibody development over time. The identified ZIKV-specific linear epitopes are valuable candidates for ZIKV-specific diagnostics. Funding Source n/a Topic Categories Viral Immunology (VIR)