Development of whole virion inactivated Kyasanur Forest Disease vaccine candidate and its preclinical safety and efficacy evaluation.

Abstract

Kyasanur Forest Disease Virus (KFDV) is a zoonotic tick-borne flavivirus that causes Kyasanur Forest Disease (KFD), a disease primarily found in India. KFD historically been confined to Karnataka state of southern India, however, in recent years, it has spread beyond its original endemic region, raising significant public health concerns. There are currently no KFD specific treatments or vaccines available. Rapid development of effective vaccine against KFD is urgently needed. We developed and evaluated a whole virion inactivated KFD virus vaccine candidate, adjuvanted with aluminum hydroxide [Al(OH)3] for its safety and efficacy in laboratory animal models. We used a well-characterized KFD virus strain and an established Vero cell platform to produce large-scale GMP-grade highly purified inactivated antigen. Two dose vaccination with the vaccine candidate (18 µg/dose) in Balb/c mice model elicited stronger IgG response and elevated neutralizing antibody as well as T cell cytokines responses and provided complete protection against KFDV challenge (100 LD). The protected mice in vaccinated group showed reduced weight loss, controlled clinical symptoms and significantly low viral load in brain tissue. Passive transfer of KFD vaccine immune serum provided effective protection to naive mice against a lethal KFDV challenge (10 LD). Single-dose and repeated-dose toxicity evaluation demonstrated that the vaccine is well tolerated, safe, and non-toxic. Our preclinical results support further advancement to human clinical trials and have obtained CDSCO approval for Phase I testing.