Cross-protection of wildtype and vaccine-derived chikungunya virus antibodies against chikungunya and Mayaro viruses in mice

Abstract The live-attenuated vaccine IXCHIQ against chikungunya virus (CHIKV) was approved in 2023, with its efficacy evaluated using human neutralizing antibody titers as surrogate effectiveness criterion. Previous in vivo studies assessed its efficacy at high CHIKV-specific antibody titers, whereas its efficacy and antibody-dependent enhancement (ADE) risks at suboptimal levels mimicking long-term immunity remain poorly characterized. Here, we assessed antibody-mediated protection following vaccination or natural infection by passively immunizing transiently immunocompromised mice with graded doses of pooled immune sera before challenge with two CHIKV genotypes or the related Mayaro virus (MAYV). Protection was evaluated using viral loads at 3 days post-infection and clinical parameters. Vaccine- and infection-induced antibodies conferred strong protection against both CHIKV genotypes, even at antibody concentrations nearing ELISA detection limits. In contrast, protection against MAYV required higher titers. We observed no ADE. Our findings align with previous studies supporting durable protection against CHIKV and partial cross-protection against MAYV.