Immune Mechanisms Involved in Schistosoma mansoni-Cathepsin B Vaccine Induced Protection in Mice

Ricciardi, Alessandra; Zelt, Nicholas; Visitsunthorn, Kittipos; Dalton, John P.; Ndao, Momar

doi:10.3389/fimmu.2018.01710

Cited by 11 publications

(11 citation statements)

References 56 publications

(66 reference statements)

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“…Finally, this study did not consider the possible role of other immune mechanisms in controlling S . mansoni infection after YS1646 infection and we have previously shown that CD4 + T cells and anti-schistosomula antibody-dependent cellular cytotoxicity (ADCC) contribute to protection after CatB immunization (± adjuvants) [56]. Studies are underway to examine these possibilities with the multi-modality YS1646-based vaccination protocols.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren’t designed to elicit a mucosal response. 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. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). 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. Serum IgG responses to CatB were monitored by ELISA. 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. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9–52.8 x103μm2) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x103μm2vs. 62.2±6.1 x103μm2: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…The SmCB + CpG vaccinated animals experienced a significant death rate (53%). Also, the Sm-cathepsin alone had a substantial success rate (41%) 25 . It seems that SmCB can help to reduce schistosomiasis for S. haematobium and S. mansoni.…”

Section: Vaccine Developmentmentioning

confidence: 99%

“…A schistosomiasis vaccine could create a long-term decrease in illness spectrum and transmission 25 . It could protect up to 600 to 700 million people 26 .…”

Section: Vaccine Developmentmentioning

confidence: 99%

“…Moreover, to control S. Mansoni schistosomiasis, Ricciardi et al 25 discovered Schistosoma mansoni Chaptesin B (SmCB) as a vaccine candidate. The authors performed in vitro killing assays in schistosomula stage parasites targets for lung-derived leukocytes and serum obtained from mice vaccinated with SmCB adjuvant with either Montanide ISA 720 VG (SEPPIC Inc., Fairfield, NJ, USA) or cytosine-guanine in the linear sequence (CpG or CG oligodeoxynucleotides) (CpG) and from mice not vaccinated.…”

Section: Vaccine Developmentmentioning

confidence: 99%

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Schistosomiasis: Life Cycle, Diagnosis, and Control

Nelwan¹

2019

Current Therapeutic Research

161

158

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Highlights Three main schistosomiasis species can infect humans; S. haematobium, S. japonicum , and S. mansoni . The parasites life cycle includes two kind of reproduction; asexual reproduction in snails and sexual reproduction in mammals. Multiple diagnostic techniques are used. Currently praziquantel is the only drug therapy approved for control of schistosomiasis but other promising candidate drugs (e.g. SpAE, and ruthenium compounds) are being tested. A number of vaccine candidates exist including SmCB1, SjAChE, and SmCB. Genetic manipulations are being investigated.

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“…In the current work we observed increases in both IFNγ and IL-5 in the multimodality PO→IM group (Fig 5), suggesting that YS1646 vaccination can induce more balanced Th1-Th2 immune response. Finally, this study did not consider the possible role of other immune mechanisms in controlling S. mansoni infection after YS1646 infection and we have previously shown that CD4 + T cells and anti-schistosomula antibody-dependent cellular cytotoxicity (ADCC) contribute to protection after CatB immunization (± adjuvants) [53]. Studies are underway to examine these possibilities with the multi-modality YS1646-based vaccination protocols.…”

Section: Discussionmentioning

confidence: 99%

Vaccination against the digestive enzyme Cathepsin B using a YS1646Salmonella entericaTyphimurium vector provides almost complete protection againstSchistosoma mansonichallenge in a mouse model

Hassan

Zelt

Perera

et al. 2019

Preprint

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24Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae 25 migrate through the lung and adult worms reside adjacent to the intestinal mucosa. None of the 26 candidate vaccines in current development is designed to elicit a mucosal response. We have 27 repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a 28 vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. 29 Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and 30 transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in 31 vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 32 3 weeks apart, using six strategies: i) saline gavage (control), ii) the 'empty' YS1646 vector orally 33 (PO) followed by intramuscular recombinant CatB (20g IM rCatB), iii) two doses of IM rCatB, 34 iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB 35 then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the 36 second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult 37 worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific 38 IgG antibodies were low/absent in the control and PO only groups but rose substantially in other 39 groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 40 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. 41 control) were 93.1% and 79.5%/90.3% respectively (all P<.0001). Granuloma size was reduced in 42 all vaccinated groups (range 32.86-52.83 x10 3 m 2 ) and most significantly in the nirB_SspH1 + 43 CatB IM group (34.74±3.35 x10 3 m 2 vs. 62.22±6.08 x10 3 m 2 : vs. control P<.01). Many eggs in 44 the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality 45 approach can provide almost complete protection against S. mansoni challenge. 46 Author Summary 47 Schistosomiasis is a parasitic disease that affects over 250 million people worldwide and over 800 48 million are at risk of infection. Of the three main species, Schistosoma mansoni is the most widely 49 distributed and is endemic in the Caribbean, South America, Africa, and the Middle East. It causes 50 a chronic disease with severe negative effects on quality of life. Mass drug administration of 51 praziquantel is the only available course of action due to a current lack of vaccines. However, 52 praziquantel does not protect from reinfection. Therefore, a vaccine would be beneficial as a long-53 term solution to reduce morbidity and transmission of the disease. Our group has repurposed the 54 attenuated YS1646 strain of Salmonella Typhimurium as an oral vaccine vector for the digestive 55 enzyme Cathepsin B of S. mansoni. Oral vaccination followed by an intramuscular dose of 56 recombinant Cathepsin B lead to significant reduction...

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Immune Mechanisms Involved in Schistosoma mansoni-Cathepsin B Vaccine Induced Protection in Mice

Cited by 11 publications

References 56 publications

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

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

Schistosomiasis: Life Cycle, Diagnosis, and Control

Vaccination against the digestive enzyme Cathepsin B using a YS1646Salmonella entericaTyphimurium vector provides almost complete protection againstSchistosoma mansonichallenge in a mouse model

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