title: HIV-1 vaccines: challenges and new perspectives.
abstract: The development of a safe and effective preventive HIV-1 vaccine remains a public health priority. Despite scientific difficulties and disappointing results, HIV-1 vaccine clinical development has, for the first time, established proof-of-concept efficacy against HIV-1 acquisition and identified vaccine-associated immune correlates of risk. The correlate of risk analysis showed that IgG antibodies against the gp120 V2 loop correlated with decreased risk of HIV infection, while Env-specific IgA directly correlated with increased risk. The development of vaccine strategies such as improved envelope proteins formulated with potent adjuvants and DNA and vectors expressing mosaics, or conserved sequences, capable of eliciting greater breadth and depth of potentially relevant immune responses including neutralizing and non-neutralizing antibodies, CD4+ and CD8+ cell-mediated immune responses, mucosal immune responses, and immunological memory, is now proceeding quickly. Additional human efficacy trials combined with other prevention modalities along with sustained funding and international collaboration remain key to bring an HIV-1 vaccine to licensure.
authors.affiliation: U.S. Military HIV Research Program; Division of Retrovirology; Walter Reed Army Institute of Research; Bethesda, MD USA; Henry M. Jackson Foundation for the Advancement of Military Medicine; Bethesda, MD USA.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Excler
authors.affiliation: U.S. Military HIV Research Program; Division of Retrovirology; Walter Reed Army Institute of Research; Bethesda, MD USA; Henry M. Jackson Foundation for the Advancement of Military Medicine; Bethesda, MD USA.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: U.S. Military HIV Research Program; Division of Retrovirology; Walter Reed Army Institute of Research; Bethesda, MD USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000302:isolation & purification*; D057134:Antibodies, Neutralizing / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D055808:Drug Discovery / Q000639:trends*; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: HIV-1; clinical trial; correlates; efficacy; licensure; public health; vaccine