Oral Presentations - Federation of Clinical Immunology Societies

S8 Abstracts
response to therapy was dominated by IL-10, but this profile did
not correlate with better preserved beta-cell function. Instead,
patients developing immunological tolerance to Diapep277
showed less decreased C-peptide production than patients
that kept a reactive phenotype. Third party control immune
responses were unaffected by therapy. No potentially adverse
immunological side effects were noted.
DiaPep277 is immunogenic in type 1 diabetic subjects and
has immune modulating properties. Immunological monitoring
allowed to distinguish therapy from placebo treatment
and could determine immunological efficacy. Tolerance to
peptide DiaPep277 may serve as immunological biomarker
measure for clinical efficacy.
doi:10.1016/j.clim.2007.03.192
OR.12 Somatic B-Cell Gene Vaccination with
Anti-DNA Ig Consensus Peptide Protects (NZB × NZW)
F1 Lupus Mice From Renal Disease
Francesca Ferrera, Postdoctoral Fellow, University of
Genova, Genova, Bevra Hahn, Professor and Chief of
Rheumatology, University of California, Los Angeles, Los
Angeles, CA, Marta Rizzi, Postdoctoral Fellow, University
of Genova, Genova, Gilberto Filaci, Associate Professor,
University of Genova, Genova, Francesco Indiveri,
Professor, University of Genova, Genova, Antonio La Cava,
Associate Professor, University of California, Los Angeles,
Los Angeles, CA, Antonio La Cava, Associate Professor
of Medicine, University of California, Los Angeles,
Los Angeles, CA
Ig molecules that participate in humoral immune responses
contain epitopes that induce T cell-mediated immune
responses. B cells process and present such epitopes and
activate T cells. We hypothesized that T cells recognizing an Ig
consensus sequence presented by B cells will modulate lupuslike
disease in mice. To test this hypothesis, NZB/W F1 lupus
mice received B cell somatic gene transfer of DNA plasmid
encoding an artificial consensus sequence mimicking T cell
determinants of murine anti-DNA IgG, or control plasmids.
Treated animals were monitored for production of antibody,
development of renal disease and phenotype, number, and
function of consensus gene-induced Tcells. It was found that the
treatment of mice with Ig consensus gene induced TGFβproducing
CD8+CD28− T cells that: (1) suppressed antigenspecific
stimulation of CD4+ Tcells in a cell-contact independent
manner; (2) reduced autoantibody production; (3) retarded the
development of nephritis, and (4) improved survival of treated
animals. Significantly, the adoptive transfer of CD8+CD28− T
cells from Ig consensus gene-protected mice into hypergammaglobulinemic
NZB/W F1 mice effectively protected the transferred
mice from development of renal disease. We conclude
that genetic expression of anti-DNA Ig consensus can induce
immunoregulatory circuits capable of delaying development of
lupus nephritis via the suppression of hypergammaglobulinemia
and renal disease.
doi:10.1016/j.clim.2007.03.193
OR.13 Therapeutic Vaccination with a Trivalent
T Cell Receptor Peptide Vaccine Induces
Peptide-specific IL-10-secreting T Cells, Restores
Deficient Foxp3 Expression, and Induces Bystander
Immunomodulation in Multiple Sclerosis Subjects
Arthur Vandenbark, Professor, Oregon Health and Science
University, Neurology, Portland, OR, Richard Bartholomew,
Executive Director of Research and Development, The
Immune Response Corporation, Carlsbad, CA, Halina
Offner, Professor, Oregon Health and Science University,
Neurology, Portland, OR, Dennis Bourdette, Professor and
Chairman, Oregon Health and Science University,
Neurology, Portland, OR
We are developing a therapeutic vaccine containing
CDR2 peptides from BV5S2, BV6S5, and BV13S1 emulsified
in IFA as a V gene-specific therapy for RR-MS. This TCR
vaccine is currently being tested in a blinded, placebocontrolled,
200 patient study with reduction of new
gadolinium enhancing lesions as the primary endpoint. We
here report new mechanistic data from a recently
completed open-label study. Immunological and clinical
parameters were followed in 27 treatment naïve and 9
previously vaccinated subjects with MS who received
monthly injections of the trivalent peptide vaccine over
1 year. TCR vaccination induced high frequencies of IL-10secreting
T cells specific for the injected TCR peptides as
well as an apparently broader pattern of anti-TCR
specificities. These regulatory specificities induced biphasic
immunomodulation that involved an initial rise
after 9 weeks of IL-10-secreting neuroantigen-specific T
cells, in conjunction with potent induction of Foxp3+ Treg
cells to normal levels after 12 weeks of treatment. These
findings are consistent with vaccine-induced stimulation of
Foxp3+ Treg cells originating from both CD25(−) and
conventional CD25(+) T cells. Restoration of previously
deficient Treg cells could explain the broad reduction of
TCR-dependent responses of both cognate T cells expressing
V genes targeted by the vaccine as well as bystander T
cells expressing different V genes, including those specific
for neuroantigens. These findings demonstrate that therapeutic
vaccination using only three commonly expressed
BV gene determinants can induce a broad immunoregulatory
network in vivo that may help control autoreactive
responses that characterize the inflammatory phase of MS.
doi:10.1016/j.clim.2007.03.194
OR.14 Mechanistic Insights Into the Differential
Efficacy of GAD65 DNA Vaccine and Anti-CD3
Combination Therapy in Treating New-Onset
Autoimmune Diabetes in RIP-LCMV and NOD Mice
Damien Bresson, Postdoctoral Fellow, La Jolla Institute for
Allergy and Immunology, La Jolla, CA, Diane Rottembourg,
Postdoctoral Fellow, La Jolla Institute for Allergy and
Immunology, La Jolla, CA, Lisa Togher, Technician, La Jolla
Institute for Allergy and Immunology, La Jolla, CA, Matthias
von Herrath, Professor, La Jolla Institute for Allergy and
Immunology, La Jolla, CA