Bacteria | Bacterial Infections and Mycoses | Biological Factors | Immunity | Immunology and Infectious Disease | Immunoprophylaxis and Therapy | Preventive Medicine | Therapeutics
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea-associated illness in developing countries. There is currently no vaccine licensed to prevent ETEC and the development of an efficacious prophylaxis would provide an intervention with significant impact. Recent studies suggested that effective protection could be achieved by inducing immunity to block colonization of ETEC. Here, we evaluated the efficacy of secretory (s) IgA2 and dimeric (d) IgA2 of an anti-colonization factor antigen antibody, 68-61, in the Aotus nancymaae non-human primate (NHP) ETEC challenge model via oral and parental delivery. Thirty-nine animals were distributed across 3 groups of 13, and challenged with 5.0×1011 cfu of H10407 on Day 0. Group 1 received a dIgA2 68-61 subcutaneously on day 0. Group 2 received a SIgA2 68-61 orally on days −1, 0, and +1, and Group 3 received an irrelevant SIgA2 antibody orally on days −1, 0, and +1. All animals were observed for symptoms of diarrhea, and stools were collected for ETEC colony counts. SIgA2 treatment significantly lowered the attack rate, resulting in a protective efficacy of 71.4% (p=0.025) in Group 2 as compared to Group 3. Anti-CfaE dIgA2 treatment group reduced the diarrheal attack rate, although the reduction did not reach significance (57.1%; P=0.072) as compared to the irrelevant SIgA2 Group 3. Our results demonstrated the feasibility of oral administration of SIgA as a potential immunoprophylaxis against enteric infections. To our knowledge, this is the first study to demonstrate the efficacy of administrated SIgA in a non-human primate model.
Immunology, Enterotoxigenic Escherichia coli (ETEC), anti-CfaE secretory IgA antibody, vaccines, prophylaxis, immunity, diarrhea, developing countries, antigens, infections
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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It is made available under a CC0 license. This article is a US Government work. It is not subject to copyright under 17 USC 105.
DOI of Published Version
bioRxiv 748442; doi: https://doi.org/10.1101/748442. Link to preprint on bioRxiv service.
Stoppato, Matteo; Gaspar, Carlos; Regeimbal, James; Nunez, Gladys; Giuntini, Serena; Gawron, Melissa A.; Pondish, Jessica R.; Martin III, Joseph C.; Schneider, Matthew; Schiller, Zachary A.; Klempner, Mark S.; Cavacini, Lisa A.; and Wang, Yang, "Oral administration of an anti-CfaE secretory IgA antibody protects against Enterotoxigenic Escherichia coli diarrheal disease in a non-human primate model" (2019). University of Massachusetts Medical School Faculty Publications. 1627.