Characterization of the T-dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) in the Göttingen minipig.
Recently, there has been a renewed interest in the use of the minipig as an alternative to dogs and non-human primates for conducting toxicological assessments in non-rodent species. Since the T-dependent antibody response (TDAR) is one of the most widely-accepted assays used in the assessment of immunocompetence, the present study was undertaken to characterize the primary and secondary TDAR to keyhole limpet hemocyanin (KLH) in the Göttingen Minipig(®). Following primary immunization with either 2 or 10 mg KLH, anti-swine IgM and IgG ELISAs were optimized and individual animal responses were evaluated over time. Immunization with 10 mg KLH on Day 0 promoted primary IgM responses that peaked 6-9 days after antigen administration, while primary IgG levels peaked on Day 13 or 14. Secondary IgG antibody levels (following secondary injection with 2 mg KLH on Day 14) plateaued on Days 20-22. Anti-KLH antibody levels were decreased in minipigs treated with cyclophosphamide (CPS), a known immunosuppressant, at doses ranging from 12.5-50 mg/kg/day, while antibody levels in animals treated with 2.5 mg CPS/kg/day were similar to levels in saline-treated swine. These results demonstrate that the Göttingen Minipig(®) can be a useful alternative non-rodent species to the dog and the non-human primate for evaluating the TDAR to KLH in regulatory assessments of immunotoxicity.
ImmunoTox®, Inc. , Richmond, VA , USA and.
Vanessa L
VL
Peachee
Matthew J
MJ
Smith
Melissa J
MJ
Beck
Donald G
DG
Stump
Kimber L
KL
White
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004285:Dogs; D006433:Hemocyanins / Q000276:immunology; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D023421:Models, Animal; D011323:Primates; D013552:Swine; D013556:Swine, Miniature; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
Immunotoxicity; TDAR; keyhole limpet hemocyanin; miniature swine; minipig