Fully human single-domain antibody targeting a highly conserved cryptic epitope on the Nipah virus G protein

Nipah virus infection, one of the top priority diseases recognized by the World Health Organization, can cause severe respiratory illness and fatal encephalitis in humans. The mortality rate is high (50-95%). A key element in combating NiV infections is the development of NiV-neutralizing antibodies. In this research, the authors utilize the platform to discover a unique NiV-neutralizing fully human single-domain antibodies (UdAb) that specifically targets a conserved cryptic epitope located at the dimeric interface of the NiV G glycoprotein. By targeting a conserved epitope on the head domain of the NiV G glycoprotein, that it may disrupt G protein tetramerization, thereby hindering F protein activation and membrane fusion. Compared to the full-length monoclonal antibody m102.4, this single-domain antibody displays significantly greater potency in inhibiting viral membrane fusion and more efficient penetration into the murine brain. As a result, this single-domain antibody has potential applications in vaccine development and shows promise as a treatment option to stop Nipah virus infections.
(DKW)