Human Experimental Challenge With Enterotoxigenic Escherichia coli Elicits Immune Responses to Canonical and Novel Antigens Relevant to Vaccine Development

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 protect...

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Bibliographic Details
Published in:The Journal of infectious diseases 2018-09, Vol.218 (9), p.1436-1446
Main Authors: Chakraborty, Subhra, Randall, Arlo, Vickers, Tim J, Molina, Doug, Harro, Clayton D, DeNearing, Barbara, Brubaker, Jessica, Sack, David A, Bourgeois, A Louis, Felgner, Philip L, Liang, Xiaowu, Mani, Sachin, Wenzel, Heather, Townsend, R Reid, Gilmore, Petra E, Darsley, Michael J, Rasko, David A, Fleckenstein, James M
Format: Article
Language:English
Subjects:
Antibodies, Bacterial - immunology
Antigens, Bacterial - immunology
Carrier Proteins - immunology
Enterotoxigenic Escherichia coli - immunology
Escherichia coli Infections - immunology
Escherichia coli Proteins - immunology
Escherichia coli Vaccines - immunology
Humans
Major and Brief Reports
Membrane Glycoproteins - immunology
Peptide Hydrolases
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Summary: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. 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. 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. 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.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiy312