Chloroform-Methanol Residue of Coxiella burnetii Markedly Potentiated the Specific Immunoprotection Elicited by a Recombinant Protein Fragment rOmpB-4 Derived from Outer Membrane Protein B of Rickettsia rickettsii in C3H/HeN Mice

PLoS One. 2015 Apr 24;10(4):e0124664. doi: 10.1371/journal.pone.0124664. eCollection 2015.

Abstract

The obligate intracellular bacteria, Rickettsia rickettsii and Coxiella burnetii, are the potential agents of bio-warfare/bio-terrorism. Here C3H/HeN mice were immunized with a recombinant protein fragment rOmp-4 derived from outer membrane protein B, a major protective antigen of R. rickettsii, combined with chloroform-methanol residue (CMR) extracted from phase I C. burnetii organisms, a safer Q fever vaccine. These immunized mice had significantly higher levels of IgG1 and IgG2a to rOmpB-4 and interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), two crucial cytokines in resisting intracellular bacterial infection, as well as significantly lower rickettsial loads and slighter pathological lesions in organs after challenge with R. rickettsii, compared with mice immunized with rOmpB-4 or CMR alone. Additionally, after challenge with C. burnetii, the coxiella loads in the organs of these mice were significantly lower than those of mice immunized with rOmpB-4 alone. Our results prove that CMR could markedly potentiate enhance the rOmpB-4-specific immunoprotection by promoting specific and non-specific immunoresponses and the immunization with the protective antigen of R. rickettsii combined with CMR of C. burnetii could confer effective protection against infection of R. rickettsii or C. burnetii.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial / immunology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / immunology*
  • Cell Line
  • Chloroform / pharmacology
  • Coxiella burnetii / drug effects
  • Coxiella burnetii / immunology*
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Immunization
  • Male
  • Methanol / pharmacology
  • Mice
  • Neutralization Tests
  • Q Fever / immunology
  • Q Fever / metabolism
  • Q Fever / pathology
  • Q Fever / prevention & control*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology*
  • Rickettsia rickettsii / immunology*

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Cytokines
  • Recombinant Proteins
  • Chloroform
  • Methanol

Grants and funding

This work was supported by the National Natural Science Foundation of China grants 31470894, 81371767 and 31170161, the Natural Science and Technology Major Project of China (grant 2013ZX10004803). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.