IMMUNIZATION OF MICE WITH DNA ENCODING FRAGMENT-C OF TETANUS TOXIN

Immunization of mice with Fragment C protein, the non-toxic C-terminal domain of tetanus toxin, will protect mice against lethal challenge w ith tetanus toxin. A plasmid, pcDNA3/tetC, which encodes a synthetic t etC gene expressed under the control of the human cytomegalovirus majo r intermediate early promoter/enhancer region, was constructed. Fragme nt C expression was observed in Chinese hamster ovary cells following transfection with pcDNA3/tetC. The immune response induced by intramus cular immunization with pure pcDNA3/tetC DNA was evaluated in a murine model. Anti-Fragment C serum immunoglobulin and proliferative respons es in splenocytes were observed following two immunizations with pcDNA 3/tetC. The major IgG subclass that recognized Fragment C was IgG2a an d the stimulated splenocytes secreted high levels of interferon-gamma. Sufficient anti-Fragment C serum immunoglobulins were induced by DNA- mediated immunization to protect mice against lethal challenge with te tanus toxin. (C) 1997 Elsevier Science Ltd.