Research

Identification of serotype-specific neutralizing epitopes on dengue envelope protein by deep mutational scanning 

Dengue fever caused by dengue virus (DENV) is the most widespread arboviral disease globally and has become one of the top ten threats to global health. It has spread to over 125 countries, causing approximately 400 million infections and 40,000 deaths annually. The burden is exceptionally high in regions like South East Asia and South Asia, which account for 70% of the cases. These reports suggest an urgent need to develop an effective dengue vaccine to prevent the disease. 

Due to the circulation of four dengue virus (DENV) serotypes, the chances of co-infection with multiple serotypes are common. Primary dengue infection elicits serotype-specific neutralizing and cross-reactive antibodies. The latter are generally non-protective and largely assist virus entry in the cells upon subsequent infection by different serotypes. This leads to antibody-mediated enhancement (ADE) of infection, a significant bottleneck in developing a universal dengue vaccine. Also, serotype-specific neutralizing antibodies are better indicators of protection. This necessitates identifying the epitopes that induce both classes of antibodies. My study aims to identify serotype-specific neutralizing epitopes on the DENV envelope using a high throughput deep mutational scanning technique. This finding can be used to design vaccine candidates without inducing cross-reactive antibodies.