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 language | English (US) |
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Pages (from-to) | 243-251 |
Number of pages | 9 |
Journal | AIDS |
Volume | 9 |
Issue number | 3 |
DOIs | |
State | Published - Mar 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