IMMUNIZATION OF MICE WITH POLIOVIRUS REPLICONS EXPRESSING THE C-FRAGMENT OF TETANUS TOXIN PROTECTS AGAINST LETHAL CHALLENGE WITH TETANUS TOXIN

In this study, we describe the construction of poliovirus genomes or ' 'replicons'' which contain the C fragment gene of tetanus toxin substi tuted for the poliovirus P1 capsid Upon transfection of replicon RNA i nto cells, we immunoprecipitated a protein corresponding to the C-frag ment of tetanus toxin using tetanus-specific antibodies. Using a recom binant vaccinia virus expressing poliovirus P1 capsid protein (VV-P1) to provide P1 protein, the replicon RNA was encapsidated; stocks of th e replicons were generated by passage with VV-P1. The immunogenicity o f the replicons was determined by immunization of transgenic mice whic h are susceptible to poliovirus. A serum antibody response to poliovir us and tetanus toroid was detected in all of the immunized mice. Prote ction against a lethal dose of tetanus toxin generally correlated with the levels of serum anti-tetanus antibodies. To address whether pre-e xisting antibodies to poliovirus limit the effectiveness of the replic on as a vaccine vector, mice were first immunized with the inactivated poliovirus vaccine followed by immunization with the replicons expres sing C-fragment protein. Anti-tetanus antibodies were detected in thes e mice after a single administration of the replicon; these antibodies conferred protection upon challenge with tetanus toxin. These results demonstrate the potential use of poliovirus replicons encoding foreig n proteins to induce a protective antibody response, even in the prese nce of pre-existing antibodies to poliovirus. (C) 1997 Published by El sevier Science Ltd.