Lennart Marcotte
Passive administration of negativing antibodies (Abs) is an seductive strategy for the control of gastrointestinal infections. still, an unanswered practical concern is the need to assure the stability of sufficient quantities of orally administered negativing Abs against intestinal pathogens (e.g., norovirus) in the harsh terrain of the gastrointestinal tract. To this end, we expressed a single- sphere Ab (VHH, nanobody) against norovirus on the cell face of Lactobacillus, a natural and salutary commensal element of the gut microbiome. First, we used intestinal epithelial cells generated from mortal convinced pluripotent stem cells to confirm that VHH 1E4 showed negativing exertion againstGII.17 norovirus. We also expressed VHH 1E4 as a cell- wall–anchored form in Lactobacillus paracasei BL23. Flow cytometry verified the expression of VHH 1E4 on the face of lactobacilli, andL. paracasei that expressed VHH 1E4 inhibited the replication ofGII.17 norovirus in vitro. We also orally administered VHH 1E4- expressingL. paracasei BL23 to origin-free BALB/ c mice and verified the presence of lactobacilli with negativing exertion in the intestine for at least 10 days after administration. therefore, cell- wall- anchored VHH- displaying lactobacilli are seductive oral nanobody deliver vectors for unresistant immunization against norovirus infection.
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