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
Citations
Student Authors
Faculty Advisor
Academic Program
UMass Chan Affiliations
Document Type
Publication Date
Subject Area
Embargo Expiration Date
Link to Full Text
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.
Source
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.