Plasma and Mucosal Immunoglobulin M, Immunoglobulin A, and Immunoglobulin G Responses to the Vibrio cholerae O1 Protein Immunome in Adults With Cholera in Bangladesh

J Infect Dis. 2017 Jul 1;216(1):125-134. doi: 10.1093/infdis/jix253.

Abstract

Background: Cholera is a severe dehydrating illness of humans caused by toxigenic strains of Vibrio cholerae O1 or O139. Identification of immunogenic V. cholerae antigens could lead to a better understanding of protective immunity in human cholera.

Methods: We probed microarrays containing 3652 V. cholerae antigens with plasma and antibody-in-lymphocyte supernatant (ALS, a surrogate marker of mucosal immune responses) from patients with severe cholera caused by V. cholerae O1 in Bangladesh and age-, sex-, and ABO-matched Bangladeshi controls. We validated a subset of identified antigens using enzyme-linked immunosorbent assay.

Results: Overall, we identified 608 immunoreactive V. cholerae antigens in our screening, 59 of which had higher immunoreactivity in convalescent compared with acute-stage or healthy control samples (34 in plasma, 39 in mucosal ALS; 13 in both sample sets). Identified antigens included cholera toxin B and A subunits, V. cholerae O-specific polysaccharide and lipopolysaccharide, toxin coregulated pilus A, sialidase, hemolysin A, flagellins (FlaB, FlaC, and FlaD), phosphoenolpyruvate-protein phosphotransferase, and diaminobutyrate-2-oxoglutarate aminotransferase.

Conclusions: This study is the first antibody profiling of the mucosal and systemic antibody responses to the nearly complete V. cholerae O1 protein immunome; it has identified antigens that may aid in the development of an improved cholera vaccine.

Keywords: HlyA; OSP; Vibrio; cholera; cholerae; immunogenic; sialidase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • Antibody Formation
  • Bangladesh / epidemiology
  • Case-Control Studies
  • Cholera / epidemiology
  • Cholera / immunology*
  • Cholera Toxin / blood
  • Female
  • Flagellin / blood
  • Humans
  • Immunity, Mucosal*
  • Immunoglobulin A / blood*
  • Immunoglobulin G / blood*
  • Immunoglobulin M / blood*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Mucous Membrane / immunology
  • O Antigens / blood
  • Phosphoenolpyruvate Sugar Phosphotransferase System / blood
  • Phosphotransferases (Nitrogenous Group Acceptor) / blood
  • Reproducibility of Results
  • Vibrio cholerae O1 / immunology*
  • Vibrio cholerae O1 / isolation & purification
  • Vibrio cholerae O139 / isolation & purification
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin M
  • O Antigens
  • Flagellin
  • Cholera Toxin
  • Phosphoenolpyruvate Sugar Phosphotransferase System
  • Phosphotransferases (Nitrogenous Group Acceptor)
  • phosphoenolpyruvate-protein phosphotransferase