Evaluation of transcutaneous immunization as a delivery route for an enterotoxigenic E. coli adhesin-based vaccine with CfaE, the colonization factor antigen 1 (CFA/I) tip adhesin

Julianne E Rollenhagen; Colleen M Woods; Aisling O'Dowd; Steven T Poole; Jing-Hui Tian; Mimi Guebre-Xabier; Larry Ellingsworth; Michael G Prouty; Greg Glenn; Stephen J Savarino

doi:10.1016/j.vaccine.2019.08.057

Evaluation of transcutaneous immunization as a delivery route for an enterotoxigenic E. coli adhesin-based vaccine with CfaE, the colonization factor antigen 1 (CFA/I) tip adhesin

Vaccine. 2019 Sep 30;37(42):6134-6138. doi: 10.1016/j.vaccine.2019.08.057. Epub 2019 Sep 3.

Affiliations

¹ Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
² Enteric Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
³ Iomai Corporation, 20 Firstfield Road, Suite 250, Gaithersburg, MD 20878, USA.
⁴ Enteric Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Electronic address: michael.g.prouty2.mil@mail.mil.
⁵ Enteric Diseases Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

PMID: 31492474
DOI: 10.1016/j.vaccine.2019.08.057

Abstract

dscCfaE is a recombinant form of the CFA/I tip adhesin CfaE, expressed by a large proportion of enterotoxigenic E. coli (ETEC). It is highly immunogenic by the intranasal route in mice and Aotus nancymaae, protective against challenge with CFA/I+ ETEC in an A. nancymaae challenge model, and antibodies to dscCfaE passively protect against CFA/I+ ETEC challenge in human volunteers. Here, we show that transcutaneous immunization (TCI) with dscCfaE in mice resulted in strong anti-CfaE IgG serum responses, with a clear dose-response effect. Co-administration with heat-labile enterotoxin (LT) resulted in enhanced immune responses over those elicited by dscCfaE alone and strong anti-LT antibody responses. The highest dose of dscCfaE administered transcutaneously with LT elicited strong HAI titers, a surrogate for the neutralization of intestinal adhesion. Fecal anti-adhesin IgG and IgA antibody responses were also induced. These findings support the feasibility of TCI for the application of an adhesin-toxin based ETEC vaccine.

Keywords: Adhesin; CFA/I; CfaE; ETEC; TCI; Transcutaneous.

Published by Elsevier Ltd.

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
Administration, Cutaneous
Animals
Bacterial Toxins / immunology*
Enterotoxigenic Escherichia coli / immunology*
Enterotoxins / immunology*
Escherichia coli Proteins / immunology*
Escherichia coli Vaccines / immunology*
Female
Fimbriae Proteins / immunology*
Immunoglobulin A / blood
Immunoglobulin A / immunology
Immunoglobulin G / blood
Immunoglobulin G / immunology
Mice
Mice, Inbred BALB C
Recombinant Proteins / immunology
Vaccination / methods*

Substances

Adhesins, Escherichia coli
Bacterial Toxins
CfaE protein, E coli
Enterotoxins
Escherichia coli Proteins
Escherichia coli Vaccines
Immunoglobulin A
Immunoglobulin G
Recombinant Proteins
Fimbriae Proteins
heat-labile enterotoxin, E coli