Kyasanur Forest Disease: feasible strategies for vaccine development and evaluation.

Kyasanur Forest Disease (KFD) is a tick-borne zoonotic infection endemic to certain parts of India, with expanding geographic distribution and recurrent focal outbreaks among forest-dependent populations in Western Ghats. The discontinuation of the formalin-inactivated KFD vaccine in 2022 has created a critical gap in prevention. New vaccine candidates are under development, but conventional Phase 3 efficacy trials are difficult to implement because of low incidence of disease, and clustered and unpredictable nature of outbreaks. KFD vaccine evaluation may require alternate regulatory approaches. An initial step would involve studies to identify candidate correlates of protection in laboratory confirmed KFD patients. These immune markers could then be evaluated in bonnet macaques challenge models to assess their association with protection against infection and clinical disease and define protective immune thresholds or composite immunological endpoints. A phase 3 immunobridging study could subsequently assess seroresponse rates against predefined immune thresholds and provide supportive evidence for vaccine efficacy and regulatory decision-making. Post-licensure studies can assess real world vaccine effectiveness and help refine vaccination strategies. Vaccine deployment should prioritise high-risk populations and align with seasonal transmission patterns of KFD. This framework may provide a feasible pathway for KFD vaccine deployment in endemic regions.