Bordetella Colonization Factor A (BcfA) Elicits Protective Immunity against Bordetella bronchiseptica in the Absence of an Additional Adjuvant

Infect Immun. 2019 Sep 19;87(10):e00506-19. doi: 10.1128/IAI.00506-19. Print 2019 Oct.

Abstract

Bordetella bronchiseptica is an etiologic agent of respiratory diseases in animals and humans. Despite the widespread use of veterinary B. bronchiseptica vaccines, there is limited information on their composition and relative efficacy and on the immune responses that they elicit. Furthermore, human B. bronchiseptica vaccines are not available. We leveraged the dual antigenic and adjuvant functions of Bordetella colonization factor A (BcfA) to develop acellular B. bronchiseptica vaccines in the absence of an additional adjuvant. BALB/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and the Bordetella antigens FHA and Prn were equally protected against challenge with a prototype B. bronchiseptica strain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine and provided protection against a B. bronchiseptica strain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection against bordetellae and other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA and Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed BALB/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single-component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines against bordetellae and other pathogens.

Keywords: BcfA; Bordetella; adjuvant; antigen; vaccines.

Publication types

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

MeSH terms

  • Adhesins, Bacterial / administration & dosage*
  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antigens, Bacterial / administration & dosage*
  • Bacterial Outer Membrane Proteins / administration & dosage*
  • Bacterial Vaccines / administration & dosage*
  • Bordetella Infections / immunology
  • Bordetella Infections / microbiology
  • Bordetella Infections / prevention & control*
  • Bordetella bronchiseptica / drug effects*
  • Bordetella bronchiseptica / immunology
  • Bordetella bronchiseptica / pathogenicity
  • Dogs
  • Female
  • Humans
  • Immunization
  • Immunogenicity, Vaccine
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th1 Cells / microbiology
  • Th1-Th2 Balance / drug effects
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / microbiology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Th2 Cells / microbiology
  • Virulence Factors, Bordetella / administration & dosage*

Substances

  • Adhesins, Bacterial
  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • FHA protein, Bordetella bronchiseptica
  • Virulence Factors, Bordetella
  • pertactin