Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice

Vaccine. 2014 Apr 11;32(18):2027-33. doi: 10.1016/j.vaccine.2014.02.057. Epub 2014 Feb 28.

Abstract

Background: Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed adhesion protein of R. rickettsii and its immunoprotection against RMSF was investigated in mice.

Methods: Recombinant Adr2 (rAdr2) was used to immunize C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after challenge with R. rickettsii. The levels of specific antibodies of sera from the immunized mice were determined and the sera from immunized mice were applied to neutralize R. rickettsii. Proliferation and cytokine secretion of CD4(+) and CD8(+) T cells isolated from R. rickettsii-infected mice were also assayed after rAdr2 stimulation.

Results: After R. rickettsii challenge, the rickettsial loads in spleens, livers, and lungs were significantly lower and the impairment degrees of these organs in rAdr2-immunized mice were markedly slighter, compared with those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2-immunized mice kept increasing during the immunization. After treatment with rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and invading host cells was significantly lower than that treated with PBS-immunized sera. Interferon-γ secretion by CD4(+) or CD8(+) T cells and tumor necrosis factor-α secretion by CD4(+) T cells from R. rickettsii-infected mice were respectively significantly greater than those from uninfected mice after rAdr2 stimulation.

Conclusion: Adr2 is a protective antigen of R. rickettsii. Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses, including efficient activity of CD4(+) and CD8(+) T cells to produce great amount of TNF-α and/or IFN-γ as well as rapid increase of specific IgG2a, which synergistically activate and opsonize host cells to killing intracellular rickettsiae.

Keywords: Adr2; Cell-mediated immunity; Rickettsia rickettsii; Rocky Mountain spotted fever; Serum neutralization..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology*
  • Bacterial Load
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G / blood
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred C3H
  • Recombinant Proteins / immunology
  • Rickettsia rickettsii / immunology
  • Rocky Mountain Spotted Fever / prevention & control*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Immunoglobulin G
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma