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 substituted for the poliovirus P1 capsid. Upon transfection of replicon RNA into cells, we immunoprecipitated a protein corresponding to the C-fragment of tetanus toxin using tetanus-specific antibodies. Using a recombinant vaccinia virus expressing poliovirus P1 capsid protein (VV-P1) to provide P1 protein, the replicon RNA was encapsidated; stocks of the replicons were generated by passage with VV-P1. The immunogenicity of the replicons was determined by immunization of transgenic mice which are susceptible to poliovirus. A serum antibody response to poliovirus and tetanus toxoid was detected in all of the immunized mice. Protection against a lethal dose of tetanus toxin generally correlated with the levels of serum anti-tetanus antibodies. To address whether pre-existing antibodies to poliovirus limit the effectiveness of the replicon as a vaccine vector, mice were first immunized with the inactivated poliovirus vaccine followed by immunization with the replicons expressing C-fragment protein. Anti-tetanus antibodies were detected in these 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 foreign proteins to induce a protective antibody response, even in the presence of pre-existing antibodies to poliovirus.
Porter
D C
DC
Department of Microbiology, University of Alabama at Birmingham 35294, USA.
Wang
J
J
Moldoveanu
Z
Z
McPherson
S
S
Morrow
C D
CD
D000818:Animals; D002478:Cells, Cultured; D005822:Genetic Vectors / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D017955:Poliovirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D012093:Replicon / Q000276:immunology*; D013744:Tetanus Toxin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D013745:Tetanus Toxoid / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D015164:Vaccines, Inactivated; C040635:tetanus toxin fragment C