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 7… Show more
“…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.…”
Section: Discussionmentioning
confidence: 98%
“…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.…”
Section: Role Of Complement In Killing Of Schistosomula In Vitromentioning
confidence: 99%
“…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.…”
Sm-p80, the large subunit of Schistosoma masoni calpain, is a leading antigen candidate for a schistosome vaccine. Prophylactic and antifecundity efficacy of Sm-p80 has been tested using a variety of vaccine approaches. However, the mechanism of Sm-p80-mediated killing is still unknown. In this study, potential role of complement in Sm-p80-mediated protection was studied using both in vitro (cobra venom factor inhibition) and in vivo using mice deficient in C3 (C3 -/-; B6.129S4-C3tm1Crr/J). In the absence of C3, Sm-p80-based vaccine was able to provide significant reduction in adult worm burden following challenge with schistosome cercariae in mice suggesting the effector functions of complement may be limited in this vaccine-induced protection.
“…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.…”
Section: Discussionmentioning
confidence: 98%
“…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.…”
Section: Role Of Complement In Killing Of Schistosomula In Vitromentioning
confidence: 99%
“…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.…”
Sm-p80, the large subunit of Schistosoma masoni calpain, is a leading antigen candidate for a schistosome vaccine. Prophylactic and antifecundity efficacy of Sm-p80 has been tested using a variety of vaccine approaches. However, the mechanism of Sm-p80-mediated killing is still unknown. In this study, potential role of complement in Sm-p80-mediated protection was studied using both in vitro (cobra venom factor inhibition) and in vivo using mice deficient in C3 (C3 -/-; B6.129S4-C3tm1Crr/J). In the absence of C3, Sm-p80-based vaccine was able to provide significant reduction in adult worm burden following challenge with schistosome cercariae in mice suggesting the effector functions of complement may be limited in this vaccine-induced protection.
“…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.…”
“…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 .…”
Schistosomiasis is a parasitic disease caused by helminths belonging to the Schistosoma genus. Approximately 700 million people are at risk of infection and 200 million people are currently infected. Schistosomiasis is the most important helminth infection, and treatment relies solely on the drug praziquantel. Worries of praziquantel resistance as well as high disease burden are only some of the justifications which support the development of a vaccine against schistosomiasis. To date, only 2 schistosome vaccines have made it into clinical trials: Sh28GST (Bilhvax) and Sm14. However, there are several vaccine candidates, such as TSP-2, sm-p8, and Sm-Cathepsin B, which are generating promising results in pre-clinical studies. Schistosomiasis vaccine development has been an uphill battle, and there are still several hurdles to overcome in the future. Fortunately, the research groups involved in the research for vaccine development have not abandoned their work. Furthermore, in the last few years, schistosomiasis has garnered some additional attention on a global scale due to its significant impact on public health.
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