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A highly immunogenic trivalent T cell receptor peptide vaccine for multiple sclerosis

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, MS Center of Excellence-West, Portland, OR, bourdett{at}ohsu.edu

E Edmonds

Department of Neurology, University of New Mexico, Albuquerque, NM

C Smith

Multiple Sclerosis Center, Swedish Medical Center, Seattle, WA, Genentech in San Francisco, CA, USA

J D Bowen

Department of Neurology, University of Washington and Department of Veterans Affairs Puget Sound Health Care System, VA MS Center of Excellence-West, Seattle, WA

C RG Guttmann

Departments of Radiology and Neurology, Center for Neurological Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Z P Nagy

Departments of Radiology and Neurology, Center for Neurological Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

J Simon

Department of Radiology, University of Colorado, Denver, CO

R Whitham

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, MS Center of Excellence-West, Portland, OR

J Lovera

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, MS Center of Excellence-West, Portland, OR

V Yadav

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, MS Center of Excellence-West, Portland, OR

M Mass

Department of Neurology, Oregon Health & Science University, Portland, OR

L Spencer

Department of Veterans Affairs Medical Center, Neuroimmunology Laboratories, Portland, OR

N Culbertson

Department of Veterans Affairs Medical Center, Neuroimmunology Laboratories, Portland, OR

R M Bartholomew

The Immune Response Corporation, Carlsbad, CA, USA

G Theofan

The Immune Response Corporation, Carlsbad, CA, USA

J Milano

The Immune Response Corporation, Carlsbad, CA, USA

H Offner

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, Neuroimmunology Laboratories, Portland, OR

A A Vandenbark

Department of Neurology, Oregon Health & Science University, Portland, OR, Department of Veterans Affairs Medical Center, Neuroimmunology Laboratories, Portland, OR

Background: T cell receptor (TCR) peptide vaccination is a novel approach to treating multiple sclerosis (MS). The low immunogenicity of previous vaccines has hindered the development of TCR peptide vaccination for MS. Objective: To compare the immunogenicity of intramuscular injections of TCR BV5S2, BV6S5 and BV13S1 CDR2 peptides in incomplete Freund’s adjuvant (IFA) with intradermal injections of the same peptides without IFA. Methods: MS subjects were randomized to receive TCR peptides/IFA, TCR peptides/saline or IFA alone. Subjects were on study for 24 weeks. Results: The TCR peptides/IFA vaccine induced vigorous T cell responses in 100% of subjects completing the 24-week study (9/9) compared with only 20% (2/10) of those receiving the TCR peptides/saline vaccine (P =0.001). IFA alone induced a weak response in only one of five subjects. Aside from injection site reactions, there were no significant adverse events attributable to the treatment. Conclusions: The trivalent TCR peptide in IFA vaccine represents a significant improvement in immunogenicity over previous TCR peptide vaccines and warrants investigation of its ability to treat MS.

Key Words: immunoregulation • multiple sclerosis • T cell receptor • vaccine

Multiple Sclerosis, Vol. 11, No. 5, 552-561 (2005)
DOI: 10.1191/1352458505ms1225oa


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