Coping with viral diversity in HIV vaccine design

PLoS Comput Biol. 2007 Apr 27;3(4):e75. doi: 10.1371/journal.pcbi.0030075.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics*
  • AIDS Vaccines / immunology*
  • Antigenic Variation / genetics*
  • Drug Design
  • Epitope Mapping / methods*
  • Gene Products, nef / genetics*
  • Gene Products, nef / immunology*
  • Genetic Variation / genetics*
  • nef Gene Products, Human Immunodeficiency Virus


  • AIDS Vaccines
  • Gene Products, nef
  • nef Gene Products, Human Immunodeficiency Virus