The Approved Live-Attenuated Chikungunya Virus Vaccine (IXCHIQ<sup>®</sup>) Elicits Cross-Neutralizing Antibody Breadth Extending to Multiple Arthritogenic Alphaviruses Similar to the Antibody Breadth Following Natural Infection
Whitney C. Weber,
Zachary J. Streblow,
Craig N. Kreklywich,
Michael Denton,
Gauthami Sulgey,
Magdalene M. Streblow,
Dorca Marcano,
Paola N. Flores,
Rachel M. Rodriguez-Santiago,
Luisa I. Alvarado,
Vanessa Rivera-Amill,
William B. Messer,
Romana Hochreiter,
Karin Kosulin,
Katrin Dubischar,
Vera Buerger,
Daniel N. Streblow
Affiliations
Whitney C. Weber
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Zachary J. Streblow
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Craig N. Kreklywich
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Michael Denton
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Gauthami Sulgey
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Magdalene M. Streblow
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Dorca Marcano
Ponce Research Institute, Ponce Health Sciences University, Ponce 00716, Puerto Rico
Paola N. Flores
Ponce Research Institute, Ponce Health Sciences University, Ponce 00716, Puerto Rico
Rachel M. Rodriguez-Santiago
Ponce Research Institute, Ponce Health Sciences University, Ponce 00716, Puerto Rico
Luisa I. Alvarado
Ponce Research Institute, Ponce Health Sciences University, Ponce 00716, Puerto Rico
Vanessa Rivera-Amill
Ponce Research Institute, Ponce Health Sciences University, Ponce 00716, Puerto Rico
William B. Messer
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239, USA
Romana Hochreiter
Valneva Austria GmbH, 1030 Vienna, Austria
Karin Kosulin
Valneva Austria GmbH, 1030 Vienna, Austria
Katrin Dubischar
Valneva Austria GmbH, 1030 Vienna, Austria
Vera Buerger
Valneva Austria GmbH, 1030 Vienna, Austria
Daniel N. Streblow
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
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.
