Treatment of experimental autoimmune arthritis by nasal administration of a type II collagen-cholera toxoid conjugate vaccine.
OBJECTIVE
To assess the efficacy of intranasal administration of microgram amounts of type II collagen (CII) coupled to cholera toxin B subunit (CTB) with respect to the development of collagen-induced arthritis, even when given after the onset of clinically evident arthropathy.


METHODS
DBA/1 mice were immunized with CII to induce arthritis and were subsequently treated with CTB-CII, CTB-conjugated ovalbumin, or CII alone. The incidence and severity of arthritis were assessed clinically and histologically.


RESULTS
Treatment with CTB-CII conjugate effectively suppressed leukocyte infiltration into the synovium and prevented bone erosion. Comparable doses of unconjugated CII administered by the same route were relatively ineffective. Protection with nasal CTB-CII vaccine was associated with decreased production of interleukin-4 (IL-4), IL-6, and interferon-gamma and with reduced CII-specific IgG1 and IgG2a antibody responses in regional lymph nodes.


CONCLUSIONS
Nasal treatment with CTB-CII appears to result in decreased peripheral Th1 and Th2 responses to collagen. These results suggest that intranasal vaccination with CTB-CII may offer an effective immunotherapeutic means for the control of chronic polyarthritis.
Tarkowski
A
A
University of Göteborg, Sweden.
Sun
J B
JB
Holmdahl
R
R
Holmgren
J
J
Czerkinsky
C
C
D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000517:prevention & control; D002772:Cholera Toxin / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D018450:Disease Progression; D000922:Immunotoxins / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D014612:Vaccines / Q000008:administration & dosage*
D001323:Autoantibodies; D000922:Immunotoxins; D014612:Vaccines; D003094:Collagen; D002772:Cholera Toxin