@article{nickle2007coping, author = {Nickle, David C. and Rolland, Morgane and Jensen, Mark A. and Pond, Sergei L. Kosakovsky and Deng, Wenjie and Seligman, Mark and Heckerman, David and Mullins, James I.}, title = {Coping with Viral Diversity in HIV Vaccine Design}, year = {2007}, month = {April}, abstract = {The ability of human immunodeficiency virus type 1 (HIV-1) to develop high levels of genetic diversity, and thereby acquire mutations to escape immune pressures, contributes to the difficulties in producing a vaccine. Possibly no single HIV-1 sequence can induce sufficiently broad immunity to protect against a wide variety of infectious strains, or block mutational escape pathways available to the virus after infection. The authors describe the generation of HIV-1 immunogens that minimizes the phylogenetic distance of viral strains throughout the known viral population (the center of tree [COT]) and then extend the COT immunogen by addition of a composite sequence that includes high-frequency variable sites preserved in their native contexts. The resulting COT+ antigens compress the variation found in many independent HIV-1 isolates into lengths suitable for vaccine immunogens. It is possible to capture 62% of the variation found in the Nef protein and 82% of the variation in the Gag protein into immunogens of three gene lengths. The authors put forward immunogen designs that maximize representation of the diverse antigenic features present in a spectrum of HIV-1 strains. These immunogens should elicit immune responses against high-frequency viral strains as well as against most mutant forms of the virus.}, url = {http://approjects.co.za/?big=en-us/research/publication/coping-viral-diversity-hiv-vaccine-design/}, pages = {e75}, journal = {PLoS Computational Biology}, }