HIV-1 vaccination administered intramuscularly can induce both systemic and mucosal T cell immunity in HIV-1-uninfected individuals.
A vaccine regimen that can rapidly control HIV-1 replication at the site of exposure following sexual contact is likely to be the most effective in preventing HIV-1 infection. As part of a larger, phase II clinical trial, we evaluated the ability of a recombinant canarypox HIV-1 vaccine to induce CTL that can be detected in both the systemic and mucosal compartments following i.m. immunization in 12 low- and high-risk HIV-1 seronegative volunteers. In the 7 volunteers receiving four immunizations with live recombinant canarypox ALVAC-HIV vaccine with or without rgp120/SF-2, HIV-1-specific CTL were detected in the blood of 5 (71%) and in the rectum of 4 (57%). CTL responses were observed in both risk strata. In contrast, 5 volunteers receiving placebo had undetectable responses in both compartments. Vaccine-induced, HIV-1-specific effector activities included IFN-gamma secretion and class I MHC-restricted CD8(+) CTL. Rectal and systemic CD8(+) CTL clones established in 1 vaccine recipient revealed similar Env-specific responses and MHC restriction. These findings indicate that parenteral vaccination can induce HIV-1-specific CTL that localize to sites of HIV-1 acquisition, where their presence may be critical in the control of initial viral replication and eventual dissemination. Determination of the optimal strategy to induce mucosal T cells requires future clinical studies.
Musey
Luwy
L
Department of Medicine, University of Washington, Seattle, WA 98195, USA.
Ding
Yan
Y
Elizaga
Marnie
M
Ha
Richard
R
Celum
Connie
C
McElrath
M Juliana
MJ
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002584:Cervix Uteri / Q000166:cytology / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004311:Double-Blind Method; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007273:Injections, Intramuscular; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; C078788:ALVAC vaccine; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D014614:Vaccines, Synthetic; D014765:Viral Vaccines