title: Coping with viral diversity in HIV vaccine design.
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.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Seattle, Washington, United States of America.
authors.forename: David C
authors.initials: DC
authors.lastname: Nickle
authors.forename: Morgane
authors.initials: M
authors.lastname: Rolland
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jensen
authors.forename: Sergei L Kosakovsky
authors.initials: SL
authors.lastname: Pond
authors.forename: Wenjie
authors.initials: W
authors.lastname: Deng
authors.forename: Mark
authors.initials: M
authors.lastname: Seligman
authors.forename: David
authors.initials: D
authors.lastname: Heckerman
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Jojic
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000940:Antigenic Variation / Q000235:genetics*; D015195:Drug Design; D018604:Epitope Mapping / Q000379:methods*; D015693:Gene Products, nef / Q000235:genetics* / Q000276:immunology*; D014644:Genetic Variation / Q000235:genetics*; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus