Oral delivery of Hyperimmune bovine serum antibodies against CS6-expressing enterotoxigenicEscherichia colias a prophylactic against diarrhea

Abstract

Background. Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A. Methods. This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 10 10 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD). Results. A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups. Conclusions. Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrumderived antibodies.

Laboratory and Field Evaluation of the Crystal VC-O1 Cholera Rapid Diagnostic Test

“…The number of colony-forming units (CFU) in the inoculum was confirmed by titrating and plating on Luria agar plates. 23 Bacterial–stool suspensions were created for nontoxigenic V. cholerae , V. cholerae non-O1, non-O139, V. cholerae O1 Ogawa, V. cholerae O1 Inaba, and V. cholerae O139 bacteria.…”

Confronting Challenges to Enterotoxigenic Escherichia coli Vaccine Development

“…A phase 1 safety and immunogenicity study of CssBA + dmLT administered IM has been completed although data on protective efficacy is currently pending. Interestingly, however administration of hyperimmune bovine IgG against recombinant CS6 did not afford significant protection against moderate to severe diarrhea upon challenge with a well-characterized CS6-producing strain B7A (122).…”

Food-Borne Biotoxin Neutralization in Vivo by Nanobodies: Current Status and Prospects

“…Nevertheless, one of the main challenges of oral administration is avoiding degradation by gastric enzymes and resistance to extreme acidic conditions. Although mAbs are highly specific, the doses required to neutralize and detoxify them are usually large, , for which Nbs, which are expressed at high levels and can be easily produced in large quantities, are advantageous. In addition, mAbs are easily denatured in the acidic pH of the stomach and by proteases, i.e., they have been degraded in the stomach and intestine into small peptides or amino acids that are subsequently absorbed.…”