Brucella melitensis 16MΔhfq attenuation confers protection against wild-type challenge in BALB/c mice

Microbiol Immunol. 2013 Jul;57(7):502-10. doi: 10.1111/1348-0421.12065.

Abstract

Brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. Although effective, the current Brucella vaccines (Rev.1 and M5-90) have several drawbacks. The first involves residual virulence for animals and humans and the second is the inability to differentiate natural infection from that caused by vaccination. Therefore, Brucella melitensis 16M hfq mutant (16MΔhfq) was constructed to overcome these drawbacks. Similarly to Rev.1 and M5-90, 16MΔhfq reduces survival in macrophages and mice and induces strong protective immunity in BALB/c mice. Moreover, these vaccines elicit anti-Brucella-specific IgG1 and IgG2a subtype responses and induce secretion of gamma interferon and interleukin-4. The Hfq antigen also allows serological differentiation between infected and vaccinated animals. These results show that 16MΔhfq is an ideal live attenuated vaccine candidate against virulent Brucella melitensis 16M infection. It will be further evaluated in sheep.

Keywords: Brucella melitensis; Hfq; live attenuated; vaccine candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Brucella Vaccine / administration & dosage
  • Brucella Vaccine / genetics
  • Brucella Vaccine / immunology*
  • Brucella melitensis / genetics
  • Brucella melitensis / immunology*
  • Brucella melitensis / pathogenicity*
  • Brucellosis / immunology
  • Brucellosis / prevention & control*
  • Cell Survival
  • Disease Models, Animal
  • Female
  • Gene Deletion*
  • Host Factor 1 Protein / genetics*
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Survival Analysis
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Virulence Factors / genetics*

Substances

  • Antibodies, Bacterial
  • Brucella Vaccine
  • Host Factor 1 Protein
  • Immunoglobulin G
  • Vaccines, Attenuated
  • Virulence Factors
  • Interleukin-4
  • Interferon-gamma