Novel diagnostic approaches for detection of Kyasanur forest disease virus

Abstract

In 1957, an epidemic broke off in the Kyasanur forest area of Karnataka state killing numerous primates. Today, this febrile illness is responsible for more than 400-500 human cases per year in India. Kyasanur Forest Disease (KFD) is one of the most understudied tick-borne disease. Recently, there has been upsurge in the number of cases with more frequent outbreaks and reports of disease coming from previous unreported areas. This should serve as a reminder about number of health concerns it poses with no therapeutic options available for combating the disease. Research on Kyasanur forest disease virus (KFDV), a flavivirus, has also been limited due to BSL 4 categorization. Accurate diagnosis of KFD still largely remains a challenge since it is often misdiagnosed as some related illnesses such as influenza, typhoid, dengue, malaria and rickettsial group of fever. A differential diagnostic tool which is sensitive, rapid and robust is critically required. In this study, we aim to target viral antigenic sites to derive pAb. KFDV EDIII domain of viral envelope protein (E) is known to carry epitopic regions for the generation of neutralizing antibodies. Other domains also induce immune response but are known to present cross-reacting antibodies. We show that KFDV EDIII is an immunodominant domain and thus can be effectively used for development of antibody-based differential diagnostic and therapeutic tool for early detection of KFD. In this project, we report that the first bleed anti-KFDV EDIII antibodies showed cross-reactivity whereas terminal bleed anti-KFDV EDIII antibodies was found to be antigen-specific and does not show cross-reactivity with DENV (1-4) and ZIKV viral antigens.