Rational design of vaccines for AIDS and influenza.

Successful immunization against challenging infectious diseases requires novel approaches to vaccine design. To control diseases of high human health impact such as AIDS and influenza by vaccination requires an understanding of the mechanisms of viral entry and identification of highly conserved vulnerable regions of the virus to which immune responses are not normally directed. Structural biology has provided important information about the three-dimensional organization and chemical structure of the HIV-1 and influenza glycoproteins. By harnessing structural biology, monoclonal antibody specificity, genomics, and informatics, we have been able to define neutralizing antibodies of exceptional breadth and potency against circulating strains of HIV-1, and we have begun to develop immunogens to elicit such antibodies. Similarly, for influenza, understanding of this target has led to structural and genetic approaches to the development of new immunogens that provide a proof of concept for universal influenza vaccination.