ABSTRACT:

Alphaviruses are emerging pathogens that can cause debilitating arthritics and neurological diseases. However, there is no approved vaccine or specific therapeutics. We determined the potencies of two anti-Chikungunya virus (CHIKV) monoclonal antibodies – CHK-124 and CHK-263 in vitro and in vivo. We showed that both two antibodies inhibit multiple processes in the virus life cycle, including attachment, membrane fusion and egress. Using cryogenic electron microscopy (cryo-EM), we determined the structure of CHIKV:CHK-124 Fab and CHIKV:CHK-263 Fab and identified the immunogenic epitopes, which explain the inhibitory mechanisms.   

In another project, the structural features of a Sindbis virus (SINV) natural mutant CH18953, which has large deletions in the E2 protein, are characterized by cryo-EM studies. The deletions cause the disorder of Domain B in E2 protein and partially exposure of fusion loop, contributing to the virus attenuation in vitro and in vivo. Furthermore, vaccination with CH18953 can induce protective response against wild type SINV in mice. Thus, the safety and immunogenicity profile of CH18953 make it a potential vaccine candidate. 

These results provide important information for vaccine and therapeutics development against alphavirus infection.

THESIS ADVISOR:  
Prof. Lok Sheemei 

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872 9249 2700

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