title: HIV-1 vaccine development: tackling virus diversity with a multi-envelope cocktail.
abstract: A major obstacle to the design of a global HIV-1 vaccine is viral diversity. At present, data suggest that a vaccine comprising a single antigen will fail to generate broadly reactive B-cell and T-cell responses able to confer protection against the diverse isolates of HIV-1. While some B-cell and T-cell epitopes lie within the more conserved regions of HIV-1 proteins, many are localized to variable regions and differ from one virus to the next. Neutralizing B-cell responses may vary toward viruses with different i) antibody contact residues and/or ii) protein conformations while T-cell responses may vary toward viruses with different (i) T-cell receptor contact residues and/or (ii) amino acid sequences pertinent to antigen processing. Here we review previous and current strategies for HIV-1 vaccine development. We focus on studies at St. Jude Children's Research Hospital (SJCRH) dedicated to the development of an HIV-1 vaccine cocktail strategy. The SJCRH multi-vectored, multi-envelope vaccine has now been shown to elicit HIV-1-specific B- and T-cell functions with a diversity and durability that may be required to prevent HIV-1 infections in humans.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA. Julia.hurwitz@stjude.org
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.forename: Scott A
authors.initials: SA
authors.lastname: Brown
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.forename: John
authors.initials: J
authors.lastname: Stambas
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Lockey
authors.forename: Robert
authors.initials: R
authors.lastname: Sealy
authors.forename: Sherri
authors.initials: S
authors.lastname: Surman
authors.forename: Pam
authors.initials: P
authors.lastname: Freiden
authors.forename: Bart
authors.initials: B
authors.lastname: Jones
authors.forename: Louis
authors.initials: L
authors.lastname: Martin
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Karen S
authors.initials: KS
authors.lastname: Slobod
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D015483:HIV Antibodies / Q000737:chemistry; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry; D006801:Humans; D007107:Immune System / Q000821:virology; D009500:Neutralization Tests; D011323:Primates
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins