Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates.
V3 loop peptide sequences from several HIV-1 strains were covalently linked to purified protein derivative (PPD) of Mycobacterium tuberculosis. A mixture of PPD conjugates of V3 loop peptides from six different strains of HIV-1 induced a stronger antibody response than a single V3 peptide-conjugate administered to guinea pigs and humans. Sera from animals immunized with a PPD-six peptide-PPD conjugate neutralized multiple primary-isolate strains of HIV-1. Potent immune responses were noted only when animals were primed with bacillus Calmette-Guerin (BCG), PPD was covalently bound to the peptides, and PPD was used as the carrier protein. Based on these animal studies, an immunogen consisting of PPD-conjugated V3 loop peptides from five HIV-1 strains was tested in 7 HIV-1 seropositive PPD skin test positive study subjects. Vaccinees exhibited over time a uniform increase in neutralizing antibodies for both laboratory adapted and primary isolates of HIV-1, including strains from multiple clades. In 3 patients with baseline viral loads between 8000 and 12,000 RNA copies/ml, the viral load declined in 2 patients to <400 copies/ml and in 1 patient to 1200 copies/ml without concurrent administration of highly active antiretroviral therapy (HAART).
Rubinstein
A
A
Department of Pediatrics, Center for AIDS Research, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA. rubinste@aecom.yu.edu
Mizrachi
Y
Y
Pettoello-Mantovani
M
M
Lenz
J
J
Liu
G Q
GQ
Rubinstein
Y
Y
Goldstein
H
H
Yust
I
I
Burke
M
M
Vardinon
N
N
Spirer
Z
Z
Cryz
S J
SJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000737:chemistry; D006168:Guinea Pigs; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D019562:Viral Load
D016915:AIDS Vaccines; D000939:Epitopes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments