Protective and antifecundity effects of Sm-p80-based DNA vaccine formulation against Schistosoma mansoni in a nonhuman primate model

Abstract

Schistosomiasis is an important parasitic disease for which there is no available vaccine. We have focused on a functionally important antigen of Schistosoma mansoni, Sm-p80, as a vaccine candidate because of its consistent immunogenicity, protective potential and antifecundity effect observed in murine models; and for its pivotal role in the immune evasion process. In the present study we report that a Sm-p80-based DNA vaccine formulation confers 38% reduction in worm burden in a nonhuman primate model, the baboon (Papio anubis). Animals immunized with Sm-p80-pcDNA3 exhibited a decrease in egg production by 32%. Sm-p80 DNA elicited specific immune responses that include IgG; its subtypes IgG1 and IgG2; and IgM in vaccinated animals. Peripheral blood mononuclear cells (PMBCs) from immunized animals when stimulated in vitro with Sm-p80 produced appreciably more Th1 response enhancing cytokines (IL-2, IFN-γ) than Th2 response enhancing cytokines (IL-4, IL-10). PBMCs produced appreciably more spot forming units for INF-γ than for IL-4 in enzyme-linked immunosorbent spot (ELISPOT) assays. Overall it appears that even though a mixed (Th1/Th2) type of humoral antibody response was generated following immunization with Sm-p80; the dominant protective immune response is Th1 type. These data reinforce the potential of Sm-p80 as an excellent vaccine candidate for schistosomiasis.

The combination of the aliphatic diamine AA0029 in ADAD vaccination system with a recombinant fatty acid binding protein could be a good alternative for the animal schistosomiasis control

“…Moreover, we observed that vaccination seems to reduce the eggs trapped in tissues per female in hamsters pointing an impairment of the oviposition capacity of the surviving females as happens in repetitive natural infections (Vercruysse and Gabriel, 2005). The anti-fecundity effect along with reduction of egg viability is considered useful for reduction transmission in schistosomiasis (Ahmad et al, 2009;Dai et al, 2014). Furthermore, a significant increase of IgG2a against SoSbAWA was observed in protected mice in vaccination experiment.…”

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

“…The resultant construct was designated as Sm-p80-VR1020. Expression of Sm-p80-VR1020 was determined by transient tranfection in COS-7 [14] and CHO K1 cells [12, 13, 15, 21]. The expressed products in COS-7 and CHO K1 cells were analyzed via polyacrylamide gel electrophoresis and western blotting, as described previously [12, 13].…”

“…An effective anti-schistosome vaccine would contribute greatly to the decrease in morbidity associated with schistosomiasis via protective immune responses leading to reduced worm burdens and decreased egg production [5–10]. To this effect, high protective and antifecundity efficacy of Sm-p80 in both murine [11–13] and nonhuman primate [14, 15] models clearly indicate that this antigen has a great potential as an important vaccine candidate for the reduction of morbidity associated with schistosome infection. Additionally, Sm-p80 was originally identified to be involved in the schistosome immune evasion process of surface membrane biogenesis [16–19], thus Sm-p80 is an important functional protein and represents a unique target to invoke protective immunity against schistosome infection.…”

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.…”