HIV-1 vaccine development: tackling virus diversity with a multi-envelope cocktail.
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.
Hurwitz
Julia L
JL
Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA. Julia.hurwitz@stjude.org
Zhan
Xiaoyan
X
Brown
Scott A
SA
Bonsignori
Mattia
M
Stambas
John
J
Lockey
Timothy D
TD
Sealy
Robert
R
Surman
Sherri
S
Freiden
Pam
P
Jones
Bart
B
Martin
Louis
L
Blanchard
James
J
Slobod
Karen S
KS
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
D016915:AIDS Vaccines; D015483:HIV Antibodies; D054298:Human Immunodeficiency Virus Proteins