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Formulation Studies to Develop Low-Cost, Orally-Delivered Secretory IgA Monoclonal Antibodies for Passive Immunization Against Enterotoxigenic Escherichia coli

Bajoria, Sakshi
Antunez, Lorena R
Kumru, Ozan S
Klempner, Mark S.
Wang, Yang
Cavacini, Lisa A
Joshi, Sangeeta B
Volkin, David B
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Abstract

Enterotoxigenic Escherichia coli (ETEC) is a common cause for diarrheal infections in children in low- and middle-income countries (LMICs). To date, no ETEC vaccine candidates have been approved. Passive immunization with low-cost, oral formulations of secretory IgA (sIgA) against ETEC is an alternative approach to protect high-risk populations in LMICs. Using a model sIgA monoclonal antibody (anti-LT sIgA2-mAb), the stability profiles of different formulations were assessed during storage and in in vitro digestion models (mimicking in vivo oral delivery). First, by employing various physicochemical techniques and a LT-antigen binding assay, three formulations with varying acid-neutralizing capacity (ANC) were evaluated to stabilize sIgA2-mAb during stress studies (freeze-thaw, agitation, elevated temperature) and during exposure to gastric phase digestion. Next, a low-volume, in vitro intestinal digestion model was developed to screen various additives to stabilize sIgA2-mAb in the intestinal phase. Finally, combinations of high ANC buffers and decoy proteins were assessed to collectively protect sIgA2-mAb during in vitro sequential (stomach to intestine) digestion. Based on the results, we demonstrate the feasibility of low-cost, 'single-vial', liquid formulations of sIgA-mAbs delivered orally after infant feeding for passive immunization, and we suggest future work based on a combination of in vitro and in vivo stability considerations.

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Bajoria S, Antunez LR, Kumru OS, Klempner M, Wang Y, Cavacini LA, Joshi SB, Volkin DB. Formulation Studies to Develop Low-Cost, Orally-Delivered Secretory IgA Monoclonal Antibodies for Passive Immunization Against Enterotoxigenic Escherichia coli. J Pharm Sci. 2023 Jul;112(7):1832-1844. doi: 10.1016/j.xphs.2023.04.005. Epub 2023 Apr 10. PMID: 37040833.

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DOI
10.1016/j.xphs.2023.04.005
PubMed ID
37040833
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© 2023 The Authors. Published by Elsevier Inc. on behalf of American Pharmacists Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)Attribution 4.0 International