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Review
. 2024 Nov;38(6):727-742.
doi: 10.1007/s40259-024-00677-y. Epub 2024 Sep 18.

Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure

Whitney C Weber  1   2 , Daniel N Streblow  1   2 , Lark L Coffey  3
Affiliations
Review

Chikungunya Virus Vaccines: A Review of IXCHIQ and PXVX0317 from Pre-Clinical Evaluation to Licensure

Whitney C Weber et al. BioDrugs. 2024 Nov.

Abstract

Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus.

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Conflict of interest statement

Whitney C. Weber, Daniel N. Streblow, and Lark L. Coffey have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Design of the IXCHIQ live attenuated vaccine (LAV). A 62-amino acid (aa) deletion was made in the chikungunya virus (CHIKV) non-structural protein (nsP) 3. The deleted region was replaced by a linker. A publishing license was granted for the image created in Biorender
Fig. 2
Fig. 2
Design of the PXVX0317 virus-like particle (VLP) vaccine. The chikungunya virus (CHIKV) non-structural genes were removed and the structural proteins: capsid, E2 and E1, along with accessory proteins E3 and 6K, were expressed from a human cytomegalovirus (CMV) R vector that comprises the human CMV early enhancer/promotor, a human T-cell leukemia virus-1 R region containing a splicing donor, a CMV immediate early-splicing acceptor, and a bovine growth hormone poly A signal. nsP is non-structural protein. A publishing license was granted for the image created in Biorender
Fig. 3
Fig. 3
Overview of IXCHIQ and PXVX0317 vaccines. Data are current as of August 30, 2024. Symptom ranges reported are compiled data for each level of symptom severity and vaccine dose across all reported clinical trials. *Indicates that the final dose has not yet been selected. CHIKV Chikungunya virus, GMT geometric mean titer, ECSA East Central South African, MAYV Mayaro virus, ONNV O’nyong nyong virus, RRV Ross River virus, US FDA US Food and Drug Administration. A publishing license was granted for the image created in Biorender
Fig. 4
Fig. 4
Global distribution of medically important alphaviruses, 2024. A publishing license was granted for the image created in Biorender
See this image and copyright information in PMC

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