Formulation Studies to Develop Low-cost, Orally-delivered Secretory IgA Monoclonal Antibodies for Passive Immunization Against Enterotoxigenic Escherichia coli (Dataset)
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Issue Date
2023Author
Bajoria, Sakshi
Antunez, Lorena R.
Kumru, Ozan S.
Klempner, Mark
Wang, Yang
Cavacini, Lisa A.
Joshi, Sangeeta B.
Volkin, David B.
Publisher
Elsevier
Type
Dataset
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
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 an 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, combination 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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