Feng Gao^†, Bette T Korber, Eric A Weaver, Hua-Xin Liao, Beatrice H Hahn and Barton F HaynesGenetic variation of HIV-1 represents a major obstacle for AIDS vaccine development. With the amino acid sequence divergence as high as 30% in envelopes between different subtypes among HIV-1 group M viruses, it is unlikely that cross-subtype protection will occur equally well among all subtypes. Computer programs have been used to generate ‘centralized’ HIV gene sequences: consensus, ancestor or center of the tree. These sequences can decrease the genetic distances between the ‘centralized’ and wild-type gene immunogens to half of those between any wild-type immuongens to each other. Recent studies demonstrated that an artificial group M consensus env gene is equidistant from any subtype and recombinants. It is biologically functional and preserves antigenicity similar to contemporary Env proteins. Most importantly, the group M consensus Env immunogen can elicit both T- and B-cell responses to wild-type HIV-1 isolates.