Structure-Based Vaccine Design Against HIV-1

Linqi Zhang of Tsinghua University in China, working with Tongqing Zhou of the National Institutes of Health in the U.S., will design a broadly protective vaccine against HIV-1 derived from the atomic structure of the viral envelope protein from the dominant transmitted founder HIV-1 strain isolated from a high-risk population in China. HIV is a rapidly evolving virus that continually alters its structure to elude the immune system and antiretroviral drugs. This makes it challenging to develop an effective vaccine. The spike-shaped envelope protein complex of HIV extends from its surface to fuse with and infect human cells. Prior to cell fusion, this complex is folded into a closed conformation and is protected from immune cells by glycan molecules. They will use the known sequence and structure of the viral envelope protein to design and synthesize stabilized pre-fusion conformations that display accessible antibody binding sites that may make them more effective vaccines. The immunogenicity of these vaccines will be tested in small animal models and non-human primates.