Immunologic responses of HIV-1-infected study subjects to immunization with a mixture of peptide protein derivative-V3 loop peptide conjugates

Arye Rubinstein, Yaffa Mizrachi, Massimo Pettoello-Mantovani, Jack Lenz, Geng Qi Liu, Yair Rubinstein, Harris Goldstein, Israel Yust, Michael Burke, Nurit Vardinon, Zvi Spirer, Stanley J. Cryz

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology
Volume22
Issue number5
Publication statusPublished - Dec 15 1999

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Keywords

  • Neutralizing antibodies
  • PPD-V3 loop conjugates
  • Primary neutralizing domain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Virology

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