The implications of patterns in HIV diversity for neutralizing antibody induction and susceptibility.
OBJECTIVE
Designing an HIV vaccine capable of eliciting broadly cross-reactive neutralizing antibodies is an extraordinarily difficult challenge. Here we focus on the implications of HIV diversity for vaccine design, detailing the impact of levels of variation in epitopes of known potent neutralizing antibodies, and summarizing patterns of overall variation in regional domains within gp120. Strategies for rational vaccine design, to enhance coverage of HIV's natural diversity, are considered.


RESULTS
Each amino acid in an envelope gp120 three-dimensional structure was grouped with its 10 nearest neighbors and classified by their natural sequence variability. Within-subtype variation is superimposed on patterns of subtype-specific variation. Regions under selection with moderate diversity are realistic vaccine targets; their variation reflects the value of escape in these regions, whereas the level of diversity is potentially approachable with a vaccine.


CONCLUSIONS
HIV diversity is so extensive that vaccine design strategies may benefit by factoring in diversity from the earliest stages, even for vaccines that target relatively conserved regions.
Korber
Bette
B
Los Alamos National Laboratory, Los Alamos, NM, USA. btk@lanl.gov
Gnanakaran
S
S
D016915:AIDS Vaccines / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D006678:HIV / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120