Prime-boost and recombinant protein vaccination strategies using Sm-p80 protects against Schistosoma mansoni infection in the mouse model to levels previously attainable only by the irradiated cercarial vaccine

Abstract

Advent of an effective schistosome vaccine would contribute significantly toward reducing the disease spectrum and transmission of schistosomiasis. We have targeted a functionally important antigen, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective and antifecundity potentials, and important role in the immune evasion process. In this study, we report that using two vaccination approaches (prime boost and recombinant protein), Sm-p80-based vaccine formulation(s) confer up to 70% reduction in worm burden in mice. Animals immunized with the vaccine exhibited a decrease in egg production by up to 75%. The vaccine elicited strong immune responses that included IgM, IgA, and IgG (IgG1, IgG2a, IgG2b, and IgG3) in vaccinated animals. Splenocytes proliferated in response to Sm-p80 produced Th1 and Th17 response enhancing cytokines. These results again emphasize the potential of Sm-p80 as a viable vaccine candidate for schistosomiasis.

Complement plays a minimal role in Sm-p80-mediated protection againstSchistosoma mansoni

“…In vitro experimentation using sera obtained from both mice 17 and baboons 21 that received Sm-p80 vaccine showed killing of schistosomula in the presence of complement. The extent of larval killing was reduced when sera were heat inactivated or CVF was introduced in the incubation media.…”

“…1). The antibodies to Sm-p80, generated in mouse and baboons, following vaccination with a Sm-p80-based vaccine formulation, 17,21 were able to kill schistosomula in vitro in the presence of exogenous complement. The complement-mediated killing effect on schistosomula was partially reversed when CVF was used; this effect was more pronounced when used with the mouse sera but not as remarkable with the baboon sera ( Fig.…”

“…15,16 Reversing the immune evasion mechanisms by vaccination with calpain is therefore an excellent target for a new schistosome vaccine. The large subunit of calpain, Sm-p80, is now a first tier vaccine candidate for S. mansoni, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] S. japonicum, 32,33 and possibly for S. hematobium 34 infections. In addition, Sm-p80 has been found to be expressed in all of the different schistosome life cycle stages 15,35,36 and, importantly, is localized in the surface syncytium, 15,37 making this host interactive protein a potential target of innate and adaptive immune responses.…”

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.…”

Still hope for schistosomiasis vaccine

“…The promising pre-clinical data in combination with the successful scale-up expression of the antigen suggest that Sm-TSP-2 is ready for Phase I trials 25 .The S. mansoni calpain large subunit, Sm-p80, another vaccine candidate is generating promising results in pre-clinical studies. Worm burden and hepatic egg burden were reduced by 70% and 75%, respectively, in mice immunized with a formulation of recombinant Sm-p80 and CpG dinucleotides compared to controls26 . The promising results observed in the mouse model, prompted the group to continue their experiments in a nonhuman primate model; the baboon.Experimentally immunized baboons had a 58% decrease in worm burden compared to the controls27 .…”