Why has an Optimally Effective Vaccine for Kyasanur Forest Disease not yetbeen achieved? A Scientific, Biological, Immunological, Ecological, andCommunity-Level Perspective

The Kyasanur forest disease (KFD) is a tick-borne disease that is endemic to Western Ghats in India. There is a formalin-inactivated vaccine for KFD virus, but it has been difficult to find one that is consistently effective or durable. Many scientific and translational factors contribute to this problem. First, the cycle of zoonotic transmission is quite complex. Second, human exposure happens episodically. Third, there is considerable genetic variation among the circulating strains of the virus. Additionally, flavivirus-specific immunological challenges such as the requirement for balanced humoral and cellular immunity and the risks of antibody-dependent enhancement, make the use of traditional vaccination platforms difficult. KAP (knowledge-attitude-practice) studies indicate that variability in vaccine acceptance and community awareness of vaccine use and booster schedules seem to be significant factors affecting real-life efficacy of vaccines. Thus, the lack of an optimally effective KFD vaccine is due to multiple facets of the complexity of KFD, rather than a lack of effort. Reverse vaccinology, immuno-informatics, and community-engaged vaccine development approaches are promising avenues for developing next-generation KFD vaccines and represent the best path for long-term, sustainable control of KFD in today’s world.