Mucosal immunogenicity and adjuvanticity of cholera toxin in swine

The oral immunogenic and adjuvant properties of cholera toxin (CT) and its nontoxic B subunit (CT-B) were assessed in swine. Both whole CT and CT-B ar e oral immunogens in swine and CT is relatively more potent. Oral administr ation of 100 mu g of CT resulted in a greater immune response than 1 mg of CT-B as measured by anti-CT-B IgA, IgG and IgM in local (jejunum) and dista nt (oral cavity) mucosal sites, and in systemic sites including blood and s pleen. Lower doses of CT were potent adjuvants for the response to CT-B, bu t did not induce detectable immunity alone. The predominant response to ora l CT-B administered with CT was intestinally produced and secreted IgA, wit h about 2500 per 10(6) jejunal lamina propria cells producing anti-CT-B IgA in immunized animals. While CT is a potent adjuvant for CT-B, its ability to act as adjuvant for heterologous proteins is more restricted. 50 mu g of CT in combination with 1 mg of CT-B did not induce antibodies to 25 mg of coadministered KLH. However, chemical linking of ovalbumin to CT-B and coad ministration with CT resulted in a detectable antibody response to ovalbumi n. These results suggest that CT is immunogenic and is a potent adjuvant fo r CT-B in swine and that the induction of mucosal immunity to heterologous antigens may require specific: targeting to the gut-associated lymphoid tis sues, (C) 1999 Elsevier Science Ltd. All rights reserved.