Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2

The large extracellular loop of the schistosoma mansoni tetraspanin,sm-tsp-2,when fused to a thioredoxin partner and formulated with freund's adjuvants,has been shown to be an efficacious vaccine against murine schistosomiasis. moreover,sm-tsp-2 is uniquely recognised by igg 1 and igg 3 from putatively resistant individuals resident in s. mansoni endemic areas in brazil. in the present study,we expressed sm-tsp-2 at high yield and in soluble form in e. coli without the need for a solubility enhancing fusion partner. we also expressed in e. coli a chimera called sm-tsp-2/5b,which consisted of sm-tsp-2 fused to the immunogenic 5b region of the hookworm aspartic protease and vaccine antigen,na-apr-1. sm-tsp-2 formulated with alum/cpg showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. sm-tsp-2/5b afforded significantly greater protection than sm-tsp-2 alone when both antigens were formulated with alum/cpg. the enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-sm-tsp-2 antibodies and il-4,il-10 and ifn-γ from spleen cells of vaccinated animals. sera from 666 individuals from brazil who were infected with s. mansoni were screened for potentially deleterious ige responses to sm-tsp-2. anti-sm-tsp-2 ige to this protein was not detected (also shown previously for na-apr-1),suggesting that the chimeric antigen sm-tsp-2/5b could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic. © 2012 pearson et al.