Structural-Based Design of HIV Vaccine Targeting the Native Conformation of Neutralizing Epitopes in gp41 MPER

Lu Lu of Shanghai Medical College, Fudan University in China working with Ling Ye of Emory University in the U.S., will design a potent HIV vaccine using selected sequences of one of the virus's envelope proteins to trigger the production of broadly neutralizing antibodies. This has been problematic due to the diversity of the viral envelope glycoprotein and its glycosylation shield, which prevent the immune system from recognizing it. The membrane-proximal external region (MPER) of the viral envelope protein has been identified as an attractive target for inducing neutralizing antibodies, and they have fused it with another viral protein to form a chimera that can partly neutralize infection. They will build on this result by modifying the structure of the MPER to stabilize it in a more active conformation, and by fusing it with slightly different viral proteins that can then be immunized altogether. They will evaluate whether this vaccine strategy further stimulates broadly neutralizing antibody production and can fully neutralize HIV in several animal models.