Sm‐p80‐based DNA vaccine formulation induces potent protective immunity against Schistosoma mansoni

Abstract

SUMMARY Although there is an effective drug (praziquantel) available for the treatment of schistosomiasis, yet the disease is still spreading unabated and is rampant in 76 countries. Control via praziquantel treatment has so far been insufficient in reducing the disease transmission. Therefore a vaccine in addition to other strategies, for example, improving sanitation and introduction of new drugs are essential to successfully control and eventually eradicate schistosomiasis. To this effect we have targeted a functionally important antigen, Sm-p80 as a vaccine candidate. In the present study, full length cDNA of Sm-p80 was cloned in VR1020, a FDA approved vector for human use. The protective efficacy of this vaccine formulation was tested in a murine model. Sm-p80-VR1020 vaccine formulation was able to induce 47% reduction in worm burden. Serology on samples obtained from vaccinated animals revealed a strong antibody response which included IgG and all of its subtypes, IgM and IgA. Proliferating splenocytes in response to recombinant Sm-p80 produced a wide spectrum of cytokines representing Th1, Th2 and Th17 types, as ascertained via RT-PCR analysis. These findings further strengthen the importance of Sm-p80 molecule as a vaccine candidate for intestinal schistosomiasis.

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

“…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.…”

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

“…and percent reduction of worm burden between control and vaccinated animals was calculated. 17,18,30 After the mice were sacrificed, liver and intestine samples were collected from each animal and digested in 4% KOH. The number of eggs present in the tissue was determined and percent reduction in egg production was calculated.…”

“…The number of eggs present in the tissue was determined and percent reduction in egg production was calculated. 17,18,30 Enzyme-linked immunosorbent assays Sera obtained following bleeding of all animals were pooled in their respective groups and ultimately used to determine antibody response. Briefly, 96-well microtiter plates were coated with 1.2 µg of recombinant Sm-p80 per well.…”

“…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.…”