Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers.
OBJECTIVE
To develop a peptide-based model for a preventive vaccine for HIV-1 infection.


METHODS
Phase I trial in HIV-1-seronegative volunteers.


METHODS
Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally.


METHODS
Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1MN (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers.


RESULTS
Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1MN prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected.


CONCLUSIONS
The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guérin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.
Rubinstein
A
A
Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Goldstein
H
H
Pettoello-Mantovani
M
M
Mizrachi
Y
Y
Bloom
B R
BR
Furer
E
E
Althaus
B
B
Que
J U
JU
Hasler
T
T
Cryz
S J
SJ
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D000915:Antibody Affinity; D003429:Cross Reactions; D015483:HIV Antibodies / Q000032:analysis* / Q000097:blood / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D012463:Saliva / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014373:Tuberculin / Q000737:chemistry* / Q000276:immunology; D014374:Tuberculin Test; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007070:Immunoglobulin A; D007074:Immunoglobulin G; C093724:PPD-MN-PND vaccine; D010446:Peptide Fragments; D014373:Tuberculin; D018074:Vaccines, Conjugate