Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers

A. Rubinstein, H. Goldstein, M. Pettoello-Mantovani, Y. Mizrachi, B. R. Bloom, E. Furer, B. Althaus, J. U. Que, T. Hasler, S. J. Cryz

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Objectives: To develop a peptide-based model for a preventive vaccine for HIV-1 infection. Design: Phase I trial in HIV-1-seronegative volunteers. Participants: 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. Interventions: Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1(MN) (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-1(MN) 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-Guerin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalAIDS
Volume9
Issue number3
StatePublished - Jan 1 1995

Keywords

  • Peptide AIDS vaccine
  • Phase I trial
  • Primary neutralizing domain
  • Purified protein derivative-conjugated peptide
  • V3 loop

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Rubinstein, A., Goldstein, H., Pettoello-Mantovani, M., Mizrachi, Y., Bloom, B. R., Furer, E., Althaus, B., Que, J. U., Hasler, T., & Cryz, S. J. (1995). Safety and immunogenicity of a V3 loop synthetic peptide conjugated to purified protein derivative in HIV-seronegative volunteers. AIDS, 9(3), 243-251.