Vaccination with a CDR2 BV6S2/6S5 peptide in adjuvant induces peptide-specific T-cell responses in patients with multiple sclerosis.

Earlier studies from several groups including ours have documented that patients with multiple sclerosis (MS) have over-expression of activated T-cells from specific TCR V beta families, including BV6S2/S5 (Kotzin et al. [1991] Proc. Natl. Acad. Sci. USA 88:9161--9165; Gold et al. [1997] J. Neuroimmunol. 76:29--38). It has also been established in the rat EAE model that peptide vaccines to the over-expressed V beta 8.2 TCR can prevent MBP induced disease (Vandenbark et al. [1989] Nature 341:541--544). In the current clinical study, 10 patients were vaccinated with 300 microg of BV6S2/6S5 peptide emulsified in incomplete Freund's adjuvant (IFA) and monitored for safety and immunogenicity in a 48-week multicenter, open-label trial. The peptide vaccine was well tolerated and no serious adverse events were observed. Vaccinations induced cell-mediated immunity to the immunizing peptide in eight of 10 patients as demonstrated by lymphocyte proliferation assay (LPA) and delayed-type hypersensitivity (DTH) skin test responses. In summary, these results demonstrate that immunization with TCR BV6S2/6S5 peptide vaccine in MS patients is safe and immunogenic, and supports a larger double-blind placebo controlled trial to determine the clinical efficacy of this approach.