Received: Accepted: OctoPublished: December 2, 2019Ĭopyright: © 2019 Hassan et al. PLoS Negl Trop Dis 13(12):Įditor: Ruifu Yang, Beijing Institute of Microbiology and Epidemiology, CHINA mansoni in a well-established murine model.Ĭitation: Hassan AS, Zelt NH, Perera DJ, Ndao M, Ward BJ (2019) Vaccination against the digestive enzyme Cathepsin B using a YS1646 Salmonella enterica Typhimurium vector provides almost complete protection against Schistosoma mansoni challenge in a mouse model. This work demonstrates that a YS1646-based, multimodality, prime-boost immunization schedule can provide nearly complete protection against S. Finally, vaccinated mice had reductions in granuloma size along with a higher proportion of morphologically-abnormal eggs. This multimodal vaccination approach also elicited both Th1 and Th2 cytokines as seen by the increases in IFNγ and IL-5. These animals had the highest titers in serum IgG and intestinal IgA antibodies. Oral vaccination followed by an intramuscular dose of recombinant Cathepsin B lead to significant reductions in parasite burden in mice. Our group has repurposed the attenuated YS1646 strain of Salmonella Typhimurium as an oral vaccine vector for the digestive enzyme Cathepsin B of S. Therefore, a vaccine would be beneficial as a long-term solution to reduce morbidity and transmission of the disease. However, praziquantel does not protect from reinfection. Mass drug administration of praziquantel is the only available course of action due to a current lack of vaccines. It causes a chronic disease with severe negative effects on quality of life. Of the three main species, Schistosoma mansoni is the most widely distributed and is endemic in the Caribbean, South America, and Africa. Schistosomiasis is a parasitic disease that affects over 250 million people worldwide and over 800 million are at risk of infection. Targeting CatB using a multi-modality approach can provide almost complete protection against S. Many eggs in the vaccinated animals had abnormal morphology. Granuloma size was reduced in all vaccinated groups (range 32.9–52.8 x10 3μm 2) and most significantly in the nirB_SspH1 + CatB IM group (34.7☓.4 x10 3μm 2vs. In this group, reductions in worm and intestine/liver egg burden (vs. The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. Serum IgG responses to CatB were monitored by ELISA. Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the ‘empty’ YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20μg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Current candidate vaccines aren’t designed to elicit a mucosal response. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Schistosoma mansoni threatens hundreds of millions of people in >50 countries.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |