Advancements in rabies immunization: transformations from early trials to cutting-edge technologies

Aims To critically evaluate current and next-generation rabies vaccine technologies and identify major barriers to eliminating rabies, an almost invariably fatal yet vaccine-preventable zoonosis causing ~59,000 deaths annually, mainly in Africa and Asia.Materials and methods A systematic review was undertaken in accordance with PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched through February 2026. Of 5,097 identified records, 136 studies satisfied eligibility criteria and were included for qualitative analysis.Results Current control relies on vaccination of humans and reservoir hosts; however, conventional vaccines are limited by cost, cold chain requirements, and multi-dose regimens. Advances in recombinant, viral vector–based, nucleic acid (DNA/mRNA), and plant-derived vaccines have improved immunogenicity and safety. DNA vaccines offer advantages in stability and safety, whereas viral vectors elicit stronger and faster immune responses; neither platform is universally preferable due to limitations in delivery efficiency, preexisting immunity, or immunogenicity. Oral and bait-based vaccines enhance feasibility for wildlife and free-roaming dog populations. However, major challenges persist, including affordability, cold chain dependence, variable immune responses, and limited accessibility in endemic regions.Conclusion Overall, improving thermostability, delivery systems, and cost-effectiveness remains critical to achieving global rabies elimination.