Current landscape with an analytical outlook: Chikungunya virus vaccine development

<p>Chikungunya virus (CHIKV), a mosquito-borne alphavirus primarily transmitted by Aedes species, continues to pose a significant global health threat due to its rapid transmission potential and debilitating arthralgia. In response to the escalating incidence and expanding geographic range, notable progress has been achieved in vaccine development. Two vaccines have received regulatory authorization: IXCHIQ (VLA1553; live-attenuated; FDA approved 9 Nov 2023; U.S. license suspended 22 Aug 2025), and VIMKUNYA (recombinant VLP; FDA accelerated approval 14 Feb 2025; commercial launch Mar 2025). These approvals represent major milestones in CHIKV prevention efforts. However, several challenges persist, including limited durability of immune protection, safety concerns in vulnerable populations, antigenic drift among circulating lineages, and the need for thermostable, globally deployable formulations. In this review, we systematically evaluate diverse vaccine platforms, including live-attenuated, inactivated, VLP, nucleic acid, and viral vector-based candidates, through a comparative analysis of immunogenicity, safety, and scalability. Furthermore, we provide strategic insights into overcoming major barriers in CHIKV vaccinology, including the risks of antibody-dependent enhancement (ADE), the challenge of achieving durable immunity, and the practical limitations of cold-chain dependency. By integrating advances in structural vaccinology and broadly neutralizing antibody development with clinical and regulatory perspectives, this review proposes a roadmap for next-generation CHIKV vaccines aimed at promoting equitable global deployment.</p>