Presented at:
7th International Congress on Neuroimunology, Venice, Italy, September 28 - Oct 2, 2004
Boosting regulatory T-cells in multiple sclerosis: immunogenicity and safety of a trivalent BV5S2, BV6S5 and BV13S1 CDR2 vaccine in incomplete Freund's adjuvant
Vandenbark A, Bartholomew R, Bourdette D
Portland, Carlsbad, USA
T cell receptor (TCR) peptide vaccination represents a novel approach to boosting regulatory T cells in multiple sclerosis (MS). Development of TCR peptide vaccination as a treatment for MS has been hindered by the relatively low immunogenicity of previously available of TCR peptide vaccines. For example, intradermal vaccination with a single CDR2 BV5S2 TCR peptide given without adjuvant induced regulatory TCR reactive T cells in 20-60% of MS subjects. In an effort to develop a more effective vaccine, we compared intramuscular injections of a trivalent TCR vaccine containing BV5S2, BV6S5 and BV13S1 CDR2 peptides emulsified in incomplete Freund’s adjuvant (IFA) with intradermal injections of the same peptides without IFA. Six monthly injections of the trivalent/IFA vaccine induced vigorous T cell responses in 100% of subjects (9/9) and was significantly more immunogenic than the peptide/saline vaccine, which induced responses in only 20% of subjects (2/10) (p=0.002). Aside from injection site reactions, there were no significant adverse events attributable to the treatment. While there were no significant clinical changes over the course of this short trial, subjects who had T cell responses to the trivalent TCR peptide vaccine showed a trend towards reduced MRI activity. The trivalent TCR peptide in IFA vaccine represents a significant improvement over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.