The Approved Live-Attenuated Chikungunya Virus Vaccine (IXCHIQ®) Elicits Cross-Neutralizing Antibody Breadth Extending to Multiple Arthritogenic Alphaviruses Similar to the Antibody Breadth Following Natural Infection

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ (R), 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.