2020
DOI: 10.1101/2020.09.02.278341
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Recombinant Paraprobiotics as a New Paradigm for Treating Gastrointestinal Nematode Parasites of Humans

Abstract: Gastrointestinal nematodes (GINs) of humans, e.g., hookworms, negatively impact childhood growth, cognition, nutrition, educational attainment, income, productivity, and pregnancy. Hundreds of millions of people are targeted with mass drug administration (MDA) of donated benzimidazole (BZ) anthelmintics. However, BZ efficacy against GINs is suboptimal, and reduced/low efficacy has been seen. Developing an anthelmintic for human MDA is daunting: it must be safe, effective, inexpensive, stable without a cold cha… Show more

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Cited by 3 publications
(25 citation statements)
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“…We recently developed a new Active Pharmaceutical Ingredient (API) containing Cry5B called IBaCC for inactivated bacterium with cytosolic crystal ( Fig. 3 A ( Li et al, 2020 )). In this form, Cry5B is expressed in a sporulation defective Bt strain under control of a non-sporulating promoter, giving rise to production of a Cry5B crystal inside a vegetative Bt cell.…”
Section: Resultsmentioning
confidence: 99%
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“…We recently developed a new Active Pharmaceutical Ingredient (API) containing Cry5B called IBaCC for inactivated bacterium with cytosolic crystal ( Fig. 3 A ( Li et al, 2020 )). In this form, Cry5B is expressed in a sporulation defective Bt strain under control of a non-sporulating promoter, giving rise to production of a Cry5B crystal inside a vegetative Bt cell.…”
Section: Resultsmentioning
confidence: 99%
“…Our data show that Cry5B crystals from IBaCC will survive the rumen and that H. contortus adults can ingest Cry5B since they are intoxicated in vitro . How Cry5B is ingested by H. contortus in the abomasum is an area for investigation but there is precedent for a blood feeder accessing Cry5B in vivo with hookworms ( Kalkofen, 1970 ; Cappello et al, 2006 ; Hu et al, 2012 , 2013b , 2018a , 2018b ; Wu et al, 2015 ; Li et al, 2020 ).…”
Section: Discussionmentioning
confidence: 99%
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“…Continuing human MDA campaigns and veterinary parasite control strategies would therefore benefit substantially with the addition of new anthelmintics against ascarid parasites with the following requirements: highly and broadly potent against this family of helminths, and safe, inexpensive, and massively scalable for MDA. We have recently described an active pharmaceutical ingredient (API) called IBaCC (see below) containing the Bacillus thuringiensis (Bt) Crystal (Cry) protein Cry5B that is effective against human hookworm infections in rodents and against Haemonchus contortus infections in sheep and that meets all the requirements for MDA [ 31 , 32 ]. Cry5B itself was shown to be active against A. suum in pigs when delivered as a live spore-crystal lysate (SCL) [ 33 ].…”
Section: Introductionmentioning
confidence: 99%