Immunological properties of allergen chemically modified with synthetic copolymer of N-vinylpyrrolidone and maleic anhydride.
Several conjugates of model allergen ovalbumin (OA) and the copolymer of N-vinyl pyrrolidone and maleic anhydride (VMA) modified with epsilon-aminocaproic acid (Acp) were prepared in different OA/Acp-VMA ratios. All conjugates were separated by ultrafiltration and analyzed by HPLC. Their compositions were determined by amino acid analysis and UV spectrometry. To detect immunogenicity, all conjugates were injected intraperitoneally into (CBAxC57BL/6)F1 mice three times in 3-week intervals in OA doses equivalent to 0.5, 10, and 100 micrograms/mouse. Only the conjugate containing 20%OA (OA(20%)-Acp-VMA) did not induce significant quantities of anti-OA IgE, but did induce anti-OA IgG antibodies in dose-dependent manner comparable to that of unmodified OA. Mixtures of OA and Acp-VMA or OA modified only with VMA without Acp activation with Acp induced dose-dependent anti-OA IgE and IgG antibody formation comparable to that of OA. Using passive cutaneous anaphylaxis, RAST inhibition and leukocyte histamine release, a significant reduction of allergenicity was noted using OA(20%)-Acp-VMA. This conjugate stimulated activation of the OA-specific T-cell hybrid 3DO-548 comparable to that of unconjugated OA. During experimental allergen-specific hyposensitization with OA(20%)-Acp-VMA, suppression of anti-OA IgE response and elevation of anti-OA IgG responses were noted when compared with unmodified OA. Selective blockade of B-cell epitopes of allergen may occur using the carrier Acp-VMA to reduce allergenicity while not affecting T-cell epitopes, thereby preserving immunogenicity. This approach of chemical modification of allergen suggests new opportunities in the creation of preparations for allergen-specific immunotherapy.
Babakhin
A A
AA
National Research Center--Institute of Immunology, Moscow, Russia.
DuBuske
L M
LM
Wheeler
A W
AW
Stockinger
B
B
Nolte
H
H
Andreev
S M
SM
Gushchin
I S
IS
Khaitov
R M
RM
Petrov
R V
RV
D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D015119:Aminocaproic Acid / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D003888:Desensitization, Immunologic / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D007274:Injections, Intraperitoneal; D008297:Male; D008299:Maleic Anhydrides / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000276:immunology*
D000485:Allergens; D008299:Maleic Anhydrides; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D010047:Ovalbumin; D015119:Aminocaproic Acid