Cytokine profiles in seronegative volunteers immunized with a recombinant canarypox and gp120 prime-boost HIV-1 vaccine. NIAID AIDS Vaccine Evaluation Group.
OBJECTIVE
To study memory T cell proliferative responses and cytokine profiles induced in HIV-1 seronegative volunteers immunized with a live recombinant canarypox vector expressing HIV-1 antigens (ALVAC-HIV) and boosted with a recombinant gp120 subunit vaccine.


METHODS
HIV-specific T cell proliferative responses and cytokines were measured 2 weeks after vaccination. Cytokines secreted by T helper 1 cells (Th1) [interleukin (IL)-2 and interferon-gamma (IFN-gamma)] and T helper 2 (Th2) cells (IL-4, IL-5, IL-6, and IL-10) were assessed both at the mRNA and the protein level.


METHODS
Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with HIV antigens. Subsequently, T cell proliferation was measured in a standard lymphoproliferation assay; secreted cytokines were measured using an enzyme-linked immunosorbent assay and upregulation of cytokine mRNA was measured using reverse transcriptase polymerase chain reaction.


RESULTS
All individuals who had received ALVAC-HIV followed by the protein vaccine exhibited HIV-1-specific T cell proliferative responses. Moreover, the PBMC of all prime-boost vaccinated individuals produced detectable IFN-gamma and IL-10 in response to stimulation with HIV-1 envelope glycoprotein antigens; 83% also had detectable levels of IL-2 and IL-6, 71% had detectable levels of IL-4, and 86% had detectable levels of IL-5.


CONCLUSIONS
These data indicate that this vaccination regimen was inducing both Th1- and Th2-type responses to HIV-1 envelope antigens. This prime-boost vaccination approach elicited T cell help for the generation of cytotoxic T lymphocyte responses as well as help for antibody production and so promises to generate a broad HIV-1-specific immune response.
Department of Medicine, University of Alabama at Birmingham, 35294-2170, USA.
S
S
Sabbaj
M J
MJ
Mulligan
R H
RH
Hsieh
R B
RB
Belshe
J R
JR
McGhee
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D018150:Avipoxvirus / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage; D018023:HIV Seronegativity / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008875:Middle Aged; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage
D016915:AIDS Vaccines; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012333:RNA, Messenger; D014614:Vaccines, Synthetic