Human experimental challenge with enterotoxigenic Escherichia coli elicits immune responses to canonical and novel antigens relevant to vaccine development

Subhra Chakraborty, Arlo Randall, Tim J. Vickers, Doug Molina, Clayton D. Harro, Barbara DeNearing, Jessica Brubaker, David A. Sack, A. Louis Bourgeois, Philip L. Felgner, Xiaowu Liang, Sachin Mani, Heather Wenzel, R. Reid Townsend, Petra E. Gilmore, Michael J. Darsley, David A. Rasko, James M. Fleckenstein

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background. Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal illness in the developing world. Enterotoxigenic E coli vaccinology has been challenged by genetic diversity and heterogeneity of canonical antigens. Examination of the antigenic breadth of immune responses associated with protective immunity could afford new avenues for vaccine development. Methods. Antibody lymphocyte supernatants (ALS) and sera from 20 naive human volunteers challenged with ETEC strain H10407 and from 10 volunteers rechallenged 4-6 weeks later with the same strain (9 of whom were completely protected on rechallenge) were tested against ETEC proteome microarrays containing 957 antigens. Results. Enterotoxigenic E coli challenge stimulated robust serum and mucosal (ALS) responses to canonical vaccine antigens (CFA/I, and the B subunit of LT) as well as a small number of antigens not presently targeted in ETEC vaccines. These included pathovar-specific secreted proteins (EtpA, EatA) as well as highly conserved E coli antigens including YghJ, flagellin, and pertactin- like autotransporter proteins, all of which have previously afforded protection against ETEC infection in preclinical studies. Conclusions. Taken together , studies reported here suggest that immune responses after ETEC infection involve traditional vaccine targets as well as a select number of more recently identified protein antigens that could offer additional avenues for vaccine development for these pathogens.

Original languageEnglish
Pages (from-to)1436-1446
Number of pages11
JournalJournal of Infectious Diseases
Volume218
Issue number9
DOIs
StatePublished - Sep 22 2018

Keywords

  • Escherichia coli
  • diarrhea
  • enterotoxigenic
  • enterotoxins
  • vaccines

Fingerprint

Dive into the research topics of 'Human experimental challenge with enterotoxigenic Escherichia coli elicits immune responses to canonical and novel antigens relevant to vaccine development'. Together they form a unique fingerprint.

Cite this