Centralized HIV-1 envelope immunogens and neutralizing antibodies.
Centralized HIV-1 genes (consensus, most recent common ancestor and center of the tree) have recently been explored for induction of broadly reactive immune responses to overcome the extraordinary genetic diversity among HIV-1 strains. Although all of these strategies are based on artificial sequences predicted by computer programs, they retain biological function, and use the CCR5 co-receptor for entry into target cells as transmitted HIV-1 Envs. Results from laboratory animals indicate that centralized immunogens are superior to many wild-type immunogens for inducing cross-subtype T and B cell immune responses. Structural modifications have improved the ability of consensus Envs to elicit antibody responses that neutralize a spectrum of HIV-1 Env pseudoviruses. However, the more difficult to neutralize tier 2 Env pseudoviruses are generally not neutralized well by anti-consensus Env antibodies, indicating the need for further modifications, new formulations, or additional strategies to generate antibodies that neutralize a full spectrum of transmitted HIV-1 strains.
Duke Human Vaccine Institute, Duke University Medical Center, Durham NC 27710, USA. fgao@duke.edu
Feng
F
Gao
Hua-Xin
HX
Liao
Beatrice H
BH
Hahn
Norman L
NL
Letvin
Bette T
BT
Korber
Barton F
BF
Haynes
D016915:AIDS Vaccines / Q000276:immunology*; D016384:Consensus Sequence / Q000235:genetics / Q000276:immunology; D015752:Genes, env / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D019713:Receptors, CCR5; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D016915:AIDS Vaccines; D019713:Receptors, CCR5; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus