Open AccessImmunologic Responses of HIV-1–Infected Study Subjects to Immunization With a Mixture of Peptide Protein Derivative–V3 Loop Peptide Conjugates
Author(s) -
Arye Rubinstein,
Yossi Mizrachi,
Massimo PettoelloMantovani,
Jack Lenz,
Geng Qi Liu,
Yair Rubinstein,
Harris Goldstein,
Israel Yust,
Michael Burke,
Nurith Vardi,
Z Spirer,
Stanley J. Cryz
Publication year - 1999
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - English
Resource type - Journals
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/00126334-199912150-00007
Subject(s) - v3 loop , immunogen , peptide , virology , conjugate , antibody , biology , epitope , immune system , immunology , monoclonal antibody , biochemistry , mathematical analysis , mathematics
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).