Vaccination and antibody prophylaxis are two main means to prevent infectious diseases. Here we describe our effort in the development of immunogens and therapeutic antibodies using structural bioinformatics approaches. For immunogen design we have stabilized HIV-1 Env trimers in the prefusion conformation, the conformation that binds to most broadly neutralizing antibodies and least non- or weakly- neutralizing antibodies, by computationally redesigning the interface of the domains that move between different conformation and improved their antigenicity, immunogenicity, and thermostability. Coupling sequences and structures, we have also identified multi-donor class broadly neutralizing antibodies targeting influenza A, which can be used as a template for the development of a universal flu vaccine. In addition, we have demonstrated that with MD simulation, antigenic determinants of a surface antigen can be computationally predicted based on conformational flexibility, antibody accessibility, and sequence conservation. In terms of antibody design we have developed a surface matrix screening approach as a general way to improve properties of antibodies, and have shown that the method improved the neutralizing potency of 10E8, an HIV-1 broadly neutralizing antibody with exceptional neutralization breadth, by more than 20 folds, which greatly reduce the cost of using this antibody as prophylaxis or treatment. These results demonstrated various important roles that structural bioinformatics can play in vaccine and antibody development.

Application of structural bioinformatics in vaccine and antibody design

254th National Meeting (2017)

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