Abstract
The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ®, referred to as VLA1553). Other pathogenic alphaviruses co-circulate with CHIKV and major questions remain regarding the potential of IXCHIQ to confer cross-protection for populations that are exposed to them. Here, we characterized the cross-neutralizing antibody (nAb) responses against heterotypic CHIKV and additional arthritogenic alphaviruses in individuals at one month, six months, and one year post-IXCHIQ vaccination. We characterized nAbs against CHIKV strains LR2006, 181/25, and a 2021 isolate from Tocantins, Brazil, as well as O'nyong-nyong virus (ONNV), Mayaro virus (MAYV), and Ross River virus (RRV). IXCHIQ elicited 100% seroconversion to each virus, with the exception of RRV at 83.3% seroconversion of vaccinees, and cross-neutralizing antibody potency decreased with increasing genetic distance from CHIKV. We compared vaccinee responses to cross-nAbs elicited by natural CHIKV infection in individuals living in the endemic setting of Puerto Rico at 8-9 years post-infection. These data suggest that IXCHIQ efficiently and potently elicits cross-nAb breadth that extends to related alphaviruses in a manner similar to natural CHIKV infection, which may have important implications for individuals that are susceptible to alphavirus co-circulation in regions of potential vaccine rollout.