translation agency

Antigen-specific suppression of anti-sulfamethoxazole antibodies in animal models.
McCall C; Gallegos A; Kehl J; McLeod D; Terhune T; Blodgett J; Cohn D;
December 30, 1994
Int Conf AIDS. 1994 Aug 7-12;10(2):152 (abstract no. PB0620). Unique

OBJECTIVE: HIV +ve patients receiving sulfamethoxazole/trimethoprim (SMX/TMP) for prophylaxis or treatment of PCP experience a high rate of hypersensitivity reactions. Many of these reactions are believed to be due to an antibody response to the SMX component of the treatment. It has been previously shown that antibody responses in mice immunized to a variety of haptens may be suppressed specifically with hapten-dextran conjugates of defined size and valence.* We wished to see if we could suppress IgG and IgE antibody titers to SMX in animals immunized to the drug. METHODS: Animals (mice, rats, rabbits, and pigs), naive or pre-immunized to SMX coupled to keyhole limpet hemocyanin (SMX-KLH) on alum, were treated s.c. with a specific immunosuppressant consisting of SMX covalently coupled to an inert scaffold molecule to give a molecular size and epitope valence shown to be non-immunogenic. Naive animals were immunized with SMX-KLH/alum the day after treatment. All animals were boosted with SMX-KLH 28-40 days after treatment. RESULTS: Animals pretreated with the antigen-specific immunosuppressant before immunization failed to mount an IgG antibody response to the SMX, although they made similar anti-KLH antibody titers as controls. Animals having pre-existing antibodies to SMX and KLH, lost their antibodies to SMX, but not to KLH, within three days of treatment. The suppression seen was long lasting (at least 28 days) and resistant to a booster immunization. The immunosuppressive SMX-scaffold molecules were also shown to be recognized by human IgG anti-SMX antibodies in sera from HIV +ve hypersensitive individuals. CONCLUSIONS: These antigen-specific immunosuppressants can prevent or abrogate an anti-SMX antibody response in animals in a long lasting and highly specific manner. They may, therefore, have utility in the management of SMX-hypersensitive patients needing prophylaxis or treatment for PCP.

Animal *Antibody Formation Epitopes/*IMMUNOLOGY IgE/BIOSYNTHESIS IgG/BIOSYNTHESIS Immunization *Immunosuppression Mice Rabbits Rats Sulfamethoxazole/ADVERSE EFFECTS/*IMMUNOLOGY Swine ABSTRACT