Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine: HLA-A3-restricted GAIA vaccine epitopes

TY - JOUR

T1 - Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine

T2 - HLA-A3-restricted GAIA vaccine epitopes

AU - De Groot, Anne S

AU - Levitz, Lauren

AU - Ardito, Matthew T

AU - Skowron, Gail

AU - Mayer, Kenneth H

AU - Buus, Soren

AU - Boyle, Christine M

AU - Martin, William D

PY - 2012/7

Y1 - 2012/7

N2 - Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8(+) cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response and that are conserved in sequence and across time may represent the "Achilles' heel" of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context of global HIV evolution. Twenty-seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs of HIV-infected donors from Providence, Rhode Island. Validation of these HLA-A3 epitopes conserved across time, clades, and geography supports the hypothesis that epitopes such as these would be candidates for inclusion in our globally relevant GAIA HIV vaccine constructs.

AB - Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8(+) cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response and that are conserved in sequence and across time may represent the "Achilles' heel" of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context of global HIV evolution. Twenty-seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs of HIV-infected donors from Providence, Rhode Island. Validation of these HLA-A3 epitopes conserved across time, clades, and geography supports the hypothesis that epitopes such as these would be candidates for inclusion in our globally relevant GAIA HIV vaccine constructs.

KW - AIDS Vaccines

KW - Computational Biology

KW - Conserved Sequence

KW - Epitopes, T-Lymphocyte

KW - HIV Infections

KW - HIV-1

KW - HLA-A3 Antigen

KW - Humans

KW - Leukocytes, Mononuclear

KW - Rhode Island

U2 - 10.4161/hv.20528

DO - 10.4161/hv.20528

M3 - Journal article

C2 - 22777092

SN - 2164-5515

VL - 8

SP - 987

EP - 1000

JO - Human Vaccines & Immunotherapeutics

JF - Human Vaccines & Immunotherapeutics

IS - 7

ER -