Durable HIV-1 antibody and T-cell responses elicited by an adjuvanted multi-protein recombinant vaccine in uninfected human volunteers.
BACKGROUND
Use of the recombinant proteins NefTat and gp120(W61D) formulated with the AS02A adjuvant system was previously shown to protect against AIDS in a rhesus macaque SHIV animal model system.


METHODS
Eighty-four HIV uninfected human participants were vaccinated intramuscularly at 0, 1, and 3 months and evaluated for safety. Immune responses were analyzed for the presence of vaccine-induced antibody and T lymphocyte responses.


RESULTS
The vaccines were safe and well tolerated at all doses. Nef-, Tat-, and gp120-specific binding antibodies were induced in all individuals that received the respective antigen, lasting up to 9 months after the final immunization. Antibodies able to neutralize the T-cell laboratory-adapted strain of HIV-1(W61D) were detected in the majority of vacinees, but did not neutralize primary isolates. Envelope-specific antibody-dependent cell cytoxicity was detected in most of the individuals receiving gp120. Robust and persistent HIV-specific lymphoproliferative responses were detected against all subunit proteins in the majority of immunized participants. As expected, HIV-specific CD8 T-cell responses were not detected.


CONCLUSIONS
Despite the lack of primary isolate neutralizing antibody induction, the observed high frequency and magnitude of other immune responses warrant further work with this vaccine or vaccine components.
Goepfert
Paul A
PA
University of Alabama at Birmingham, 908 20th Street South, CCB 328, Birmingham, AL 35294, USA. paulg@uab.edu
Tomaras
Georgia D
GD
Horton
Helen
H
Montefiori
David
D
Ferrari
Guido
G
Deers
Mark
M
Voss
Gerald
G
Koutsoukos
Marguerite
M
Pedneault
Louise
L
Vandepapeliere
Pierre
P
McElrath
M Juliana
MJ
Spearman
Paul
P
Fuchs
Jonathan D
JD
Koblin
Beryl A
BA
Blattner
William A
WA
Frey
Sharon
S
Baden
Lindsey R
LR
Harro
Clayton
C
Evans
Thomas
T
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000917:Antibody Formation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000009:adverse effects / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000032:analysis; D017780:Malaria Vaccines / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D017780:Malaria Vaccines; C493155:RTS,S-AS02A vaccine; D014614:Vaccines, Synthetic; D007371:Interferon-gamma