Exploratory study on Th1 epitope-induced protective immunity against Coxiella burnetii infection

PLoS One. 2014 Jan 30;9(1):e87206. doi: 10.1371/journal.pone.0087206. eCollection 2014.

Abstract

Coxiella burnetii is a Gram-negative bacterium that causes Q fever in humans. In the present study, 131 candidate peptides were selected from the major immunodominant proteins (MIPs) of C. burnetii due to their high-affinity binding capacity for the MHC class II molecule H2 I-A(b) based on bioinformatic analyses. Twenty-two of the candidate peptides with distinct MIP epitopes were well recognized by the IFN-γ recall responses of CD4(+) T cells from mice immunized with parental proteins in an ELISPOT assay. In addition, 7 of the 22 peptides could efficiently induce CD4(+) T cells from mice immunized with C. burnetii to rapidly proliferate and significantly increase IFN-γ production. Significantly higher levels of IL-2, IL-12p70, IFN-γ, and TNF-α were also detected in serum from mice immunized with a pool of the 7 peptides. Immunization with the pool of 7 peptides, but not the individual peptides, conferred a significant protection against C. burnetii infection in mice, suggesting that these Th1 peptides could work together to efficiently activate CD4(+) T cells to produce the Th1-type immune response against C. burnetii infection. These observations could contribute to the rational design of molecular vaccines for Q fever.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Coxiella burnetii / immunology*
  • Epitopes / immunology*
  • Female
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-2 / immunology
  • Mice
  • Mice, Inbred C57BL
  • Q Fever / immunology*
  • Th1 Cells / immunology*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Epitopes
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interferon-gamma

Grants and funding

This research was supported by grants (81371767 and 31170161) from the National Natural Science Foundation of China, a grant (2010CB530200/2010CB530205) from the National Basic Research Program of China, and a grant (2013ZX10004803) from the National Science and Technology Major Project of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.