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.
Morgan
E E
EE
The Immune Response Corporation, Carlsbad, California 92008, USA.
Nardo
C J
CJ
Diveley
J P
JP
Kunin
J
J
Bartholomew
R M
RM
Moss
R B
RB
Carlo
D J
DJ
D000328:Adult; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; D005620:Freund's Adjuvant