Currently submitted to: JMIR Research Protocols
Date Submitted: Mar 5, 2026
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Real-world effectiveness, safety, immunogenicity and cost effectiveness of the IXCHIQ® chikungunya vaccine: an ambispective cohort study in La Réunion, CHIK RE VAC study, DGOS N° ECTZ347081
ABSTRACT
Background:
Chikungunya virus (CHIKV) is a mosquito-borne arbovirus that causes acute febrile illness frequently associated with severe polyarthralgia and long-term disabling sequelae. In 2024–2025, La Réunion Island experienced a major resurgence of CHIKV transmission after more than a decade without documented autochthonous circulation. The live-attenuated chikungunya vaccine VLA1553 (IXCHIQ®, Valneva) was recently approved based primarily on immunogenicity data and a validated immune correlate of protection. However, real-world evidence regarding vaccine effectiveness, safety, and population-level impact during active outbreaks remains limited.
Objective:
The CHIK-RE-VAC study aims to evaluate the real-world effectiveness, safety, immunogenicity, and cost-effectiveness of the VLA1553 chikungunya vaccine during an ongoing epidemic on La Réunion Island.
Methods:
CHIK-RE-VAC is an ambispective, observational, multicenter, phase IV cohort study conducted across hospital and outpatient care clusters on La Réunion Island. Eligible adults are enrolled into vaccinated and unvaccinated groups according to their decision to receive vaccination in accordance with national recommendations. The study integrates both prospective recruitment and a retrospective cohort of individuals vaccinated prior to study initiation. Participants are followed for up to 12 months after vaccination or index date with active surveillance, including weekly symptom monitoring and triggered clinical visits. The primary outcome is vaccine effectiveness against laboratory-confirmed symptomatic chikungunya infection at 6 and 12 months. Secondary outcomes include severe disease, hospitalization, adverse events following vaccination, persistent symptoms, health-related quality of life, vaccine acceptability, and cost-effectiveness. A nested immunogenicity substudy evaluates neutralizing antibody responses and cellular immune responses over time. Statistical analyses will use propensity score–based weighting and generalized estimating equation models accounting for clustering.
Results:
Recruitment began in April 2025 following the launch of a government-funded vaccination campaign targeting populations at high risk of severe chikungunya. An amendment introducing a retrospective cohort was approved in July 2025 to include individuals vaccinated prior to study initiation and to enhance recruitment and statistical power. As of March 2026, 260 participants have been enrolled across the prospective and retrospective components. Recruitment and follow-up are ongoing.
Conclusions:
The CHIK-RE-VAC study will provide the first comprehensive real-world evaluation of the effectiveness, safety, immunogenicity, and cost-effectiveness of the VLA1553 chikungunya vaccine during an active epidemic. The findings are expected to inform vaccination strategies, public health preparedness, and policy decisions regarding the deployment of chikungunya vaccines in outbreak settings. Clinical Trial: EU Clinical Trials Register: EU-CT 2025-521307-43-00; ClinicalTrials.gov: NCT06928753.
Citation
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