Identification and characterization of human monoclonal antibodies for immunoprophylaxis against enterotoxigenic Escherichia coli infection
Date
2018-08-01Journal
Infection and ImmunityPublisher
American Society for MicrobiologyType
Article
Metadata
Show full item recordAbstract
Enterotoxigenic Escherichia coli (ETEC) causes diarrheal illness in infants in the developing world and travelers to countries where the disease is endemic, including military personnel. ETEC infection of the host involves colonization of the small intestinal epithelium and toxin secretion, leading to watery diarrhea. There is currently no vaccine licensed to prevent ETEC infection. CFA/I is one of the most common colonization factor antigens (CFAs). The CFA/I adhesin subunit, CfaE, is required for ETEC adhesion to host intestinal cells. Human antibodies against CfaE have the potential to block colonization of ETEC and serve as an immunoprophylactic against ETEC-related diarrhea. Mice transgenic for human immunoglobulin genes were immunized with CfaE to generate a panel of human monoclonal IgG1 antibodies (HuMAbs). The most potent IgG1 antibodies identified in the in vitro functional assays were selected and isotype switched to secretory IgA (sIgA) and tested in animal colonization assays via oral administration. Over 300 unique anti-CfaE IgG1 HuMAbs were identified. The lead IgG1 anti-CfaE HuMAbs completely inhibited hemagglutination and blocked adhesion of ETEC to Caco-2 cells. Epitope mapping studies revealed that HuMAbs recognized epitopes in the N-terminal domain of CfaE near the putative receptor binding site. Oral administration of anti-CfaE antibodies in either IgG or sIgA isotypes inhibited intestinal colonization in mice challenged with ETEC. A 2- to 4-log decrease in CFU was observed in comparison to mice challenged with irrelevant isotype controls. We identified fully human monoclonal antibodies against the CfaE adhesion domain that can be potentially employed as an immunoprophylactic to prevent ETEC-related diarrhea.Description
Correction for this article is at https://www.doi.org/10.1128/IAI.00713-18Sponsors
This work was supported by the Defense Advanced Research Project Agency (DARPA-BAA-13-03) and the Bill & Melinda Gates Foundation (OPP1173647).Identifier to cite or link to this item
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054936549&origin=inward; http://hdl.handle.net/10713/9860ae974a485f413a2113503eed53cd6c53
10.1128/IAI.00355-18
Scopus Count
Collections
Related articles
- Enterotoxigenic Escherichia coli Adhesin-Toxoid Multiepitope Fusion Antigen CFA/I/II/IV-3xSTa(N12S)-mnLT(G192G/L211A)-Derived Antibodies Inhibit Adherence of Seven Adhesins, Neutralize Enterotoxicity of LT and STa Toxins, and Protect Piglets against Diarrhea.
- Authors: Nandre R, Ruan X, Lu T, Duan Q, Sack D, Zhang W
- Issue date: 2018 Mar
- Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design.
- Authors: Amcheslavsky A, Wallace AL, Ejemel M, Li Q, McMahon CT, Stoppato M, Giuntini S, Schiller ZA, Pondish JR, Toomey JR, Schneider RM, Meisinger J, Heukers R, Kruse AC, Barry EM, Pierce BG, Klempner MS, Cavacini LA, Wang Y
- Issue date: 2021 Feb 2
- Immunogenicity of a prototype enterotoxigenic Escherichia coli adhesin vaccine in mice and nonhuman primates.
- Authors: Sincock SA, Hall ER, Woods CM, O'Dowd A, Poole ST, McVeigh AL, Nunez G, Espinoza N, Miller M, Savarino SJ
- Issue date: 2016 Jan 4
- Preclinical Characterization of Immunogenicity and Efficacy against Diarrhea from MecVax, a Multivalent Enterotoxigenic E. coli Vaccine Candidate.
- Authors: Seo H, Garcia C, Ruan X, Duan Q, Sack DA, Zhang W
- Issue date: 2021 Jun 16
- Antibodies induced by enterotoxigenic Escherichia coli (ETEC) adhesin major structural subunit and minor tip adhesin subunit equivalently inhibit bacteria adherence in vitro.
- Authors: Seo H, Nandre RM, Nietfeld J, Chen Z, Duan Q, Zhang W
- Issue date: 2019