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Research

Challenges in understanding and generating protective antibodies to highly variable human viruses

Highly variable viruses including hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have developed structural features in their envelope spikes to escape antibodies.  In natural infection, most antibodies elicited to the envelope spikes are directed to highly variable regions of non-neutralizing epitopes.  These antibodies are ineffective against viral quasispecies.  Consequently, vaccine candidates designed to mimic natural infection will not likely elicit protective antibodies.  To overcome the challenge of viral diversity, the humoral components of any candidate vaccines should aim to elicit neutralizing antibodies targeting conserved regions on the envelope spikes.  Broadly neutralizing antibodies, i.e. antibodies that can cross-neutralize diverse viral isolates, define critical epitopes for antibody protection against highly variable viruses.

In our laboratory, we are interested in the strategies and technologies to discover novel broadly neutralizing antibodies and to elicit them in immunization.  Current research topics are:

(1) Discovery and improvement of broadly neutralizing antibodies to HCV and other highly variable viruses.

(2) Dissecting antibody responses to HCV in natural infection and vaccination.

(3) Understanding molecular mechanisms of virus neutralization by antibodies.

We believe the above research efforts will allow us to identify more broadly neutralizing epitopes in disease-causing viruses and the expanding list of epitopes should improve our chance of developing immunogens to elicit protective antibody responses.