Key Positions of HIV-1 Env and Signatures of Vaccine Efficacy Show Gradual Reduction of Population Founder Effects at the Clade and Regional Levels
Changze Han, Jacklyn Johnson, Rentian Dong, Raghavendranath Kandula, Alexa Kort, Maria Wong, Tianbao Yang, Patrick Breheny, Grant Brown, Hillel Haim
Abstract
The Env protein of HIV-1 is the primary target in AIDS vaccine design. Frequent mutations in the virus increase the number of Env forms in each population, limiting the efficacy of AIDS vaccines. Comparison of newly emerging forms in different populations showed that each position of Env is evolving toward a specific combination of amino acids. Similar changes are occurring in different HIV-1 subtypes and geographic regions toward the same position-specific combinations of amino acids, often from distinct ancestral sequences. The predictable nature of HIV-1 Env evolution, as shown here, provides a new framework for designing vaccines that are tailored to the unique combination of variants expected to emerge in each virus subtype and geographic region.