Cerebrospinal fluid cell phenotypic analysis from a phase 2 trial of the BHT-3009 DNA vaccine for multiple sclerosis

• Published in: Multiple sclerosis 2008-09, Vol.14, p.S54-S54
• Main Authors: Nadj, C, Nadj, I, Havrdova, E, Krasulova, E, Selmaj, K, Losy, J, Radue, E-W, Gianettoni, J, Solvason, N, Tersini, K, Valone, F, Utz, P J, Robinson, W H, Steinman, L, Garren, H
• Format: Article
• Language: English
• ISSN: 1352-4585

Background: BHT-3009 is a tolerizing DNA vaccine for multiple sclerosis (MS), encoding full-length human myelin basic protein. In a 48-week phase 2 trial of relapsing-remitting MS patients, BHT-3009 was shown to cause antigen-specific immune tolerance and to reduce brain lesions in patients with high cerebrospinal fluid (CSF) IgG levels at baseline. Objective: The objective of the current study is to examine the CSF of patients treated with BHT-3009 for any changes in immuno-logical activity. Methods: Two hundred eighty-nine relapsing-remitting MS patients were randomized to placebo, 0.5 mg BHT-3009, or 1.5 mg BHT-3009, given approximately every 4 weeks until week 44. CSF from 80 of these patients at baseline and week 44 were analyzed by fluorescence-activated cell sorting (FACS) stains for various cell-surface markers of immunological activity. Results: Several significant changes in immune cell populations were noted in the placebo group from baseline to week 44. For example, there was a decrease in CD25+/CD8+ cells from 13.4% at baseline to 5.2% at week 44 with placebo (p=0.03), which could represent a relative reduction of Treg cells. With BHT-3009 there was no statistically significant change (from 7% to 9.7% on 0.5 mg, from 10.8% to 4.2% on 1.5 mg). There was also an increase in CD26+/CD3+ cells from 18.6% at baseline to 49.8% at week 44 (p=0.004) and in CD80+/CD8+ cells from 2.7% at baseline to 16.6% at week 44 (p=0.018) with placebo, which could represent an increase in the activation of T cells. With BHT-3009 there was no statistically significant change in either of these cell types (CD26+/CD3+ cells: from 16.1% to 31.3% on 0.5 mg, from 20% to 33.6% on 1.5 mg; CD80+/CD8+ cells: from 15.6% to 14.2% on 0.5 mg, from 9.9% to 12% on 1.5 mg). Conclusions: These data, as well as others which will be presented, could suggest a relative activation of immune cell populations within the placebo group compared with the BHT-3009 groups.