Carbohydrate-based particles: a new adjuvant for allergen-specific immunotherapy.
The occurrence of systemic anaphylactic side-effects in the course of allergen-specific immunotherapy has been strongly reduced by the adsorption of allergens to aluminium hydroxide, the most frequently used adjuvant in humans. Using the major timothy grass pollen allergen, Phl p 5b, in its recombinant form for immunization of mice, we demonstrate that carbohydrate-based particles (CBP) exhibit several potential advantages over aluminium-hydroxide as adjuvant for immunotherapy. Similar to alum-bound rPhl p 5b, CBP-bound rPhl p 5b induced a stronger antibody and cytokine response than unbound rPhl p 5b after subcutaneous injection in mice. The antibodies induced by CBP-bound rPhl p 5b, exhibited potentially beneficial activities as they cross-reacted with group 5 allergens from five other grass species and inhibited the binding of grass pollen allergic patients IgE to Phl p 5b. Alum-bound rPhl p 5b induced a preferential allergen-specific Th2-response characterized by high immunoglobulin G1 (IgG1) antibody levels and elevated interleukin (IL)-4 and IL-5 production in cultured splenocytes. By contrast, CBP-bound rPhl p 5b, but not rPhl p 5b alone or coadministered with CBP, induced a mixed allergen-specific T helper 1 (Th1)/Th2 immune response characterized by the additional production of allergen-specific IgG2a/b antibody responses and elevated interferon-gamma production. Conjugation of rPhl p 5b to CBP yielded a stable vaccine formulation with preserved immunogenic features of the allergen and, in contrast to alum, induced no granulomatous tissue reactions. Based on these results, CBP is suggested as a potentially useful adjuvant for specific immunotherapy of IgE-mediated allergies.
Grönlund
Hans
H
Unit of Clinical Immunology and Allergy, Karolinska Institutet, Stockholm, Sweden. hans.gronlund@ks.se
Vrtala
Susanne
S
Wiedermann
Ursula
U
Dekan
Gerhard
G
Kraft
Dietrich
D
Valenta
Rudolf
R
Van Hage-Hamsten
Marianne
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000473:pathology / Q000628:therapy; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D000485:Allergens; D002241:Carbohydrates; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E