title: The HIV-1 gp120 V1V2 loop: structure, function and importance for vaccine development.
abstract: Although the second variable loop (V2) of the HIV-1 gp120 envelope glycoprotein shows substantial sequence diversity between strains, its functional importance imposes critical conservation of structure, and within particular microdomains, of sequence. V2 influences HIV-1 viral entry by contributing to trimer stabilization and co-receptor binding. It is one of 4 key domains targeted by the broadly neutralizing antibodies that arise during HIV-1 infection. HIV-1 uses V1V2 sequence variation and glycosylation to escape neutralizing antibody. In the Thai Phase III HIV-1 vaccine trial, RV144, vaccine-induced IgG against V1V2 inversely correlated with the risk of HIV-1 acquisition, and HIV-1 strains infecting RV144 vaccine recipients differed from those infecting placebo recipients in the V2 domain. Similarly, non-human primate challenge studies demonstrated an inverse correlation between vaccine-induced anti-V2 responses and simian immunodeficiency virus acquisition. We hypothesize that increased magnitude, frequency and duration of vaccine-induced anti-V2 antibody responses should improve efficacy afforded by pox-protein prime-boost HIV vaccine strategies.
authors.affiliation: Armed Forces Research Institute of Medical Sciences (AFRIMS), 315/6 Rajvithi Road, Bangkok 10400, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D011323:Primates
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV vaccine; RV144; V1V2 loop; efficacy; gp120; neutralizing antibodies; nonneutralizing antibodies