Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection againstSchistosomamansoniInfection Comparable to Those Achieved by the Irradiated Cercarial Vaccine

Abstract

No vaccine is available to prevent human schistosomiasis to date. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In this study we report that a Sm-p80-based DNA vaccine formulation, in a human use approved vector (VR1020), confers 46% reduction in worm burden in the baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 showed 28% decrease in egg production following challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust antigen specific immune responses that included IgG; its subtypes IgG1 and IgG2; IgA and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) and splenocytes from baboons vaccinated with Sm-p80-VR1020 when stimulated in vitro with recombinant Sm-p80 produced considerably higher levels of Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced significantly higher number of spot forming units (SFU) for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. A mixed Th1/Th2 type of humoral and T cell responses were generated following immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.

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 order to isolate trapped schistosome eggs, the livers, intestines and bladder (hamster only) of the euthanized mice and hamsters were also collected and digested overnight in 5% potassium hydroxide (Tucker et al 2013). Egg burden in these tissues were determined as described previously (Ahmad et al 2009a; Ahmad et al 2009b; Tucker et al 2013; Zhang et al 2010b). …”

“…Serum samples were obtained by centrifugation after blood was allowed to clot at room temperature. Antibody response following vaccination was measured by Enzyme-Linked Immunosorbent Assay (ELISA) as previously described (Le et al 2014; Zhang et al 2010b). Briefly, 96-well plates were coated with rSm-p80 (1.2 μg/well).…”

Schistosomiasis vaccines

“…At present, to our knowledge, Sm-p80 is the sole schistosome vaccine candidate that has been tested for its prophylactic, antifecundity and therapeutic efficacy in different vaccine formulations and approaches (e.g., naked DNA alone; recombinant protein with adjuvants; and prime with DNA, followed by boosting with protein plus adjuvants) in two experimental animal models (mouse and baboon) of infection and disease. 16,[50][51][52][53][54][55][56][57][58][59][60][61][62] Furthermore, the validity of Sm-p80 as a viable vaccine candidate has been reinforced by the work of five "research groups" who have independently demonstrated reproducible and consistent protective efficacy in mice following challenge infection using calpain or its peptides as an antigen (Nagoya City University Medical School, Nagoya, Japan; 63 [50][51][52][53][54][55][56][57][58][59][60][61][62] ). Sm-p80-based vaccine formulations have three protective effects: worm reduction, antifecundity effect and protection against acute schistosomiasis.…”

Bilharzia: Pathology, Diagnosis, Management and Control

“…Two randomised double-blind control vaccine trials were performed in buffaloes to determine the efficacy levels of the SjCTPI (TPI) and the SjC23 (Tetraspanin) vaccines, both on their own, and fused together with the dendritic cell targeting molecule, heat-shock protein 70 (Hsp70) (SjCTPI-Hsp70 and SjC23-Hsp70). The most successful vaccine construct was the SjCTPI-Hsp70, which produced a 51.2% reduction in worm burden, a 61.5% reduction in liver eggs, a 52.1% reduction in faecal eggs and a 52.1% reduction in the hatching of faecal miracidia [114,115]. These are very important findings because buffalo account for approximately 80% of the transmission to humans for S. japonicum in China and the Philippines [13-20].…”