Enhanced Protective Efficacy of a Chimeric Form of the Schistosomiasis Vaccine Antigen Sm-TSP-2

Abstract

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 IgG1 and IgG3 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.

Cross-species prophylactic efficacy of Sm-p80-based vaccine and intracellular localization of Sm-p80/Sm-p80 ortholog proteins during development in Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium

“…In the RA model, co-administration of IL-12 (a potent Th1 inducing cytokine) with RA vaccine resulted in almost sterile immunity which was associated with a high induction of IFN-γ in an autocrine manner (Wilson and Coulson 2009; Wilson et al 1999; Wilson et al 2016). Studies by our group and other colleagues have shown that the production of IFN-γ is associated with protection against schistosome infection in animal models (Ahmad et al 2009c; Le et al 2014; Pearson et al 2012; Varaldo et al 2004; Zhang et al 2011). The protective role of TNF-α against schistosomiasis has also been demonstrated by the RA vaccine model (Street et al 1999).…”

Lipid core peptide targeting the cathepsin D hemoglobinase ofSchistosoma mansonias a component of a schistosomiasis vaccine

“…44 Further studies should therefore incorporate Sm-A 263 K into a P25 bearing multiepitope LCP-based vaccine with protective epitopes from other lead vaccine antigens including Sm-TSP-2, Smp80-calpain 45 and Sh-GST28.…”

Urinary schistosomiasis

“…Development of an effective vaccine has the potential for making a considerable impact. A chimeric vaccine fusion of the antigens for both hookworm and Schistosoma parasites (Sm-TSP-2 and Na-APR-1) was recently used successfully in an experimental murine challenge study [43]. This vaccine is particularly suitable for use in areas with endemicity for both diseases.…”