View All Abstracts for Session 10
46 Phase I Clinical Trial of a Multivalent HIV-1 Peptide Vaccine Containing B and T Epitopes Formulated in Incomplete Freund’s Adjuvant
B. Graham*1, J. Ottinger2, K. Weinhold2, G. Ferrari2, M. Keefer3, J. McElrath4, and B. Haynes2
1Vaccine Res. Ctr., NIH, Bethesda, MD, USA; 2Duke Univ. Med. Ctr., Durham, NC, USA; 3Rochester Univ. Sch. of Med. and Dentistry, NY, USA; and 4Univ. of Washington Sch. of Med. at Seattle, USA
Background: A peptide vaccine was produced containing B- and T-cell epitopes from the V3 and C4 envelope domains of 4 subtype B HIV-1 isolates (MN, RF, CanO, and Ev91). The peptide mixture was formulated as an emulsion in incomplete Freund’s adjuvant (IFA).
Methods: Low-risk, healthy adult subjects were enrolled in a randomized, placebo-controlled dose-escalation study and were selected using criteria that 50% in each study group would be HLA-B7+. Immunizations were scheduled at 0, 1, and 6 months using a total peptide dose of 1 or 4 mg. Serum and cryopreserved PBMC from 16 vaccine recipients and 2 placebo recipients after the second immunization were evaluated by neutralization assays and IFN-g responses to vaccine component peptides in newly formatted ELISPOT and ICC assays optimized to assess CD4+ and CD8+ lymphocyte responses. In addition, standard 51Cr release assays were performed on fresh PBMC specimens obtained from the same volunteers.
Results: Twenty-four subjects were enrolled; 18 completed 2 injections. The study was prematurely terminated because 4 vaccinees developed prolonged pain and sterile abscess formation at the injection site: 2 after dose 1, and 2 after dose 2. The immunogenicity assessments showed that 6/8 vaccinees at each dose level had detectable MN-specific NT activity, and 2/6 HLA-B7+ vaccinees had classical CD8+ CTL activity detected. However, using both ELISPOT and ICC, 8/16 vaccinees and 0/2 controls had detectable vaccine-specific CD8+ T-cell responses. 6/8 responders had moderate or severe systemic reactions to immunization or sterile abscess formation, whereas only 3/8 nonresponders had moderate systemic reactions.
Conclusions: This is the first peptide-based HIV vaccine with significant immunogenicity. However, as currently formulated with IFA, there is unacceptable reactogenicity. The severity of local and systemic reactions appears to correlate better with T cell than antibody responses. In addition, we show combining multiple measures of T-cell response improves the assessment of vaccine-induced immunogenicity.
Contact Author about this Abstract
