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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.

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.

SUBMITTER: Weber WC

PROVIDER: S-EPMC11359099 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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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.

Weber Whitney C WC Streblow Zachary J ZJ Kreklywich Craig N CN Denton Michael M Sulgey Gauthami G Streblow Magdalene M MM Marcano Dorca D Flores Paola N PN Rodriguez-Santiago Rachel M RM Alvarado Luisa I LI Rivera-Amill Vanessa V Messer William B WB Hochreiter Romana R Kosulin Karin K Dubischar Katrin K Buerger Vera V Streblow Daniel N DN

Vaccines 20240807 8

The first vaccine against chikungunya virus (CHIKV) was recently licensed in the U.S., Europe, and Canada (brand IXCHIQ<sup>®</sup>, 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 o ...[more]

PMID: 39204019

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Project description:Host cells respond to viral infections by producing type I interferon (IFN), which induces the expression of hundreds of interferon-stimulated genes (ISGs). Although ISGs mediate a protective state against many pathogens, the antiviral functions of the majority of these genes have not been identified. IFITM3 is a small transmembrane ISG that restricts a broad range of viruses, including orthomyxoviruses, flaviviruses, filoviruses, and coronaviruses. Here, we show that alphavirus infection is increased in Ifitm3(-/-) and Ifitm locus deletion (Ifitm-del) fibroblasts and, reciprocally, reduced in fibroblasts transcomplemented with Ifitm3. Mechanistic studies showed that Ifitm3 did not affect viral binding or entry but inhibited pH-dependent fusion. In a murine model of chikungunya virus arthritis, Ifitm3(-/-) mice sustained greater joint swelling in the ipsilateral ankle at days 3 and 7 postinfection, and this correlated with higher levels of proinflammatory cytokines and viral burden. Flow cytometric analysis suggested that Ifitm3(-/-) macrophages from the spleen were infected at greater levels than observed in wild-type (WT) mice, results that were supported by experiments with Ifitm3(-/-) bone marrow-derived macrophages. Ifitm3(-/-) mice also were more susceptible than WT mice to lethal alphavirus infection with Venezuelan equine encephalitis virus, and this was associated with greater viral burden in multiple organs. Collectively, our data define an antiviral role for Ifitm3 in restricting infection of multiple alphaviruses.The interferon-induced transmembrane protein 3 (IFITM3) inhibits infection of multiple families of viruses in cell culture. Compared to other viruses, much less is known about the antiviral effect of IFITM3 on alphaviruses. In this study, we characterized the antiviral activity of mouse Ifitm3 against arthritogenic and encephalitic alphaviruses using cells and animals with a targeted gene deletion of Ifitm3 as well as deficient cells transcomplemented with Ifitm3. Based on extensive virological analysis, we demonstrate greater levels of alphavirus infection and disease pathogenesis when Ifitm3 expression is absent. Our data establish an inhibitory role for Ifitm3 in controlling infection of alphaviruses.

Dataset Information

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.

Publications

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.

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

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.

Publications

The Approved Live-Attenuated Chikungunya Virus Vaccine (IXCHIQ&lt;sup&gt;®&lt;/sup&gt;) Elicits Cross-Neutralizing Antibody Breadth Extending to Multiple Arthritogenic Alphaviruses Similar to the Antibody Breadth Following Natural Infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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 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.