Soluble antigens derived from Coxiella burnetii elicit protective immunity in three animal models without inducing hypersensitivity

Cell Rep Med. 2021 Dec 6;2(12):100461. doi: 10.1016/j.xcrm.2021.100461. eCollection 2021 Dec 21.

Abstract

Q fever is caused by the intracellular bacterium Coxiella burnetii, for which there is no approved vaccine in the United States. A formalin-inactivated whole-cell vaccine (WCV) from virulent C. burnetii NMI provides single-dose long-lived protection, but concerns remain over vaccine reactogenicity. We therefore sought an alternate approach by purifying native C. burnetii antigens from the clonally derived avirulent NMII strain. A soluble bacterial extract, termed Sol II, elicits high-titer, high-avidity antibodies and induces a CD4 T cell response that confers protection in naive mice. In addition, Sol II protects against pulmonary C. burnetii challenge in three animal models without inducing hypersensitivity. An NMI-derived extract, Sol I, enhances protection further and outperforms the WCV gold standard. Collectively, these data represent a promising approach to design highly effective, non-reactogenic Q fever vaccines.

Keywords: Aerosol; C57BL/6; Coxiella burnetii; Guinea pig; Hypersensitivity; LPS; Primate; Solubilized; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aerosols
  • Animals
  • Antibody Affinity
  • Antigenic Variation
  • Antigens, Bacterial / immunology*
  • Bacterial Vaccines / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Coxiella burnetii / immunology*
  • Disease Models, Animal
  • Female
  • Guinea Pigs
  • Hypersensitivity / immunology*
  • Immunity*
  • Immunization
  • Lipopolysaccharides
  • Lung / microbiology
  • Lung / pathology
  • Macaca mulatta
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Q Fever / immunology*
  • Q Fever / microbiology
  • Q Fever / prevention & control*
  • Solubility

Substances

  • Aerosols
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Lipopolysaccharides