Cross-Reactivity, Epitope Mapping, and Potency of Monoclonal Antibodies to Class 5 Fimbrial Tip Adhesins of Enterotoxigenic Escherichia coli

Yang Liu; Sakina Shahabudin; Sami Farid; Lanfong H Lee; Annette L McVeigh; Milton Maciel Jr.,; Steven T Poole; Matthew Broadman; Michael G Prouty; Stephen J Savarino

doi:10.1128/IAI.00246-20

Cross-Reactivity, Epitope Mapping, and Potency of Monoclonal Antibodies to Class 5 Fimbrial Tip Adhesins of Enterotoxigenic Escherichia coli

Infect Immun. 2020 Oct 19;88(11):e00246-20. doi: 10.1128/IAI.00246-20. Print 2020 Oct 19.

Authors

Affiliations

¹ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA yang.liu2.ctr@mail.mil.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
³ U.S. Naval Medical Research Unit No. 3, Cairo, Egypt.
⁴ Enteric Diseases Department, Naval Medical Research Center, Silver Spring, Maryland, USA.
⁵ Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Abstract

Enterotoxigenic Escherichia coli (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of the class 5 fimbrial family being the best characterized. The eight related members of the ETEC class 5 fimbrial family are subdivided into three subclasses (5a, 5b, and 5c) that share similar structural arrangements, including a fimbrial tip adhesin. However, sequence variability among the class 5 adhesins may hinder the generation of cross-protective antibodies. To better understand functional epitopes of the class 5 adhesins and their ability to induce intraclass antibody responses, we produced 28 antiadhesin monoclonal antibodies (MAbs) to representative adhesins CfaE, CsbD, and CotD, respectively. We determined the MAb cross-reactivities, localized the epitopes, and measured functional activities as potency in inhibition of hemagglutination induced by class 5 fimbria-bearing ETEC. The MAbs' reactivities to a panel of class 5 adhesins in enzyme-linked immunosorbent assays (ELISAs) revealed several reactivity patterns, including individual adhesin specificity, intrasubclass specificity, intersubclass specificity, and class-wide cross-reactivity, suggesting that some conserved epitopes, including two conserved arginines, are shared by the class 5 adhesins. However, the cross-reactive MAbs had functional activities limited to strains expressing colonization factor antigen I (CFA/I), coli surface antigen 17 (CS17), or CS1, suggesting that the breadth of functional activities of the MAbs was more restricted than the repertoire of cross-reactivities measured by ELISA. The results imply that multivalent adhesin-based ETEC vaccines or prophylactics need more than one active component to reach broad protection.

Keywords: ETEC; enterotoxigenic Escherichia coli; fimbrial tip adhesin; monoclonal antibodies.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adhesins, Escherichia coli / immunology*
Animals
Antibodies, Bacterial / immunology
Antibodies, Monoclonal / immunology*
Antigens, Bacterial / immunology
Cross Reactions / immunology*
Enterotoxigenic Escherichia coli / immunology*
Epitope Mapping
Female
Mice
Mice, Inbred BALB C

Substances

Adhesins, Escherichia coli
Antibodies, Bacterial
Antibodies, Monoclonal
Antigens, Bacterial