Recombinant vaccinia viruses and gene gun vectors expressing the large subunit of Schistosoma mansoni calpain used in a murine immunization-challengemodel

Schistosomiasis is a parasitic disease affecting over 200 million people ev ery year in tropical regions of the world. Drug treatment and other existin g control measures are costly and have failed to eliminate the incidence of infection, morbidity and mortality due to Schistosoma mansoni infection. V accination of susceptible individuals using recombinant vaccines encoding k ey S. mansoni antigens may be the most effective and least expensive means of controlling schistosomiasis. A candidate vaccine antigen is p80, the lar ge subunit of the S. mansoni protease, calpain. In our vaccine studies, we have employed both the wild-type p80 and a mutant p80 (mut p80) in which an active site amino acid was genetically altered to create a less proteolyti cally-active enzyme. Two vaccine delivery approaches were implemented using p80 or mut p80 as vaccine antigen: recombinant vaccinia virus (RVV) inocul ation and DNA immunization via the Accell(R) gene gun (GG) delivery system. RVV's expressing p80 and mut p80 were generated and tested for recombinant protein expression in vitro. These RW's were tested for protective capacit y in mouse challenge studies. Neither subcutaneous nor intranasal vaccinati ons with RVV-p80 or RVV-mut p80 were capable of significantly reducing the mean worm burdens of vaccinated mice. A GG-RVV combination immunization reg ime using WRG-vectors encoding p80 and mut p80 for GG priming and the RVV's for boosting prior to S. mansoni challenge infection was performed and no significant protection was obtained over two repeated studies. However, dup licate challenge studies involving GG immunization of mice with WRG-vectors encoding p80 or mut p80 revealed that 3 inoculations of mice with WRG-full 5' mut p80 (containing the full 5' untranslated region of mut p80) provided 60% protection which was statistically significant (p < 0.05). These preliminary in vivo studies demonstrate the potential for further stu dy of the protection afforded by gene gun-delivered WRG-full5' mut p80 into subsequently-challenged mice. Such studies may pave the way to effective v accination of humans using WRG DNA vectors expressing a schistosomal calciu m-activated neutral protease. (C) 1999 Elsevier Science Ltd, All rights res erved.