Identification of Chlamydia trachomatis Antigens Recognized by T Cells From Highly Exposed Women Who Limit or Resist Genital Tract Infection

J Infect Dis. 2016 Dec 15;214(12):1884-1892. doi: 10.1093/infdis/jiw485. Epub 2016 Oct 12.

Abstract

Background: Natural infection induces partial immunity to Chlamydia trachomatis Identification of chlamydial antigens that induce interferon γ (IFN-) secretion by T cells from immune women could advance vaccine development.

Methods: IFN-γ production by CD4+ and CD8+ peripheral blood T cells from 58 high-risk women was measured after coculture with antigen-presenting cells preincubated with recombinant Escherichia coli expressing a panel of 275 chlamydial antigens. Quantile median regression analysis was used to compare frequencies of IFN-γ responses in women with only cervical infection to those in women with endometrial infection and frequencies in women who remained uninfected for over 1 year to those in women who developed incident infection. Statistical methods were then used to identify proteins associated with protection.

Results: A higher median frequency of CD8+ T-cell responses was detected in women with lower genital tract chlamydial infection, compared with those with upper genital tract chlamydial infection (13.8% vs 9.5%; P =04), but the CD4+ T-cell response frequencies were not different. Women who remained uninfected displayed a greater frequency of positive CD4+ T-cell responses (29% vs 18%; P < .0001), compared with women who had incident infection, while the frequencies of CD8+ T-cell responses did not differ. A subset of proteins involved in central metabolism, type III secretion, and protein synthesis were associated with protection.

Conclusions: Investigations in naturally exposed women reveal protective responses and identify chlamydial vaccine candidate antigens.

Keywords: Chlamydia trachomatis; antigen; genital; vaccine; women.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Cells, Cultured
  • Chlamydia Infections / immunology*
  • Chlamydia Infections / prevention & control*
  • Chlamydia trachomatis / immunology*
  • Coculture Techniques
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Longitudinal Studies
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Reproductive Tract Infections / immunology*
  • T-Lymphocytes / immunology*
  • Young Adult

Substances

  • Antigens, Bacterial
  • Recombinant Proteins
  • Interferon-gamma