Two Bordetella bronchiseptica attenuated vaccine candidates confer protection against lethal challenge with B. Bronchiseptica and Pasteurella multocida toxin in mouse models

Yue Zhang, Lin Lin, Jie Yang, Qingjie Lv, Mixue Wang, Fei Wang, Xi Huang, Lin Hua, Xiangru Wang, Huanchun Chen, Brenda A. Wilson, Bin Wu, Zhong Peng

Research output: Contribution to journalArticlepeer-review

Abstract

Dermonecrotic toxin (DNT) is an important bacterial virulence factor produced by the zoonotic pathogens Bordetella bronchiseptica and Pasteurella multocida. This study aims to explore the possibility of expressing different fragments of P. multocida toxin (PMT) in the chromosome of attenuated B. bronchiseptica to generate single-component mucosal vaccine candidates. To achieve this, a 954-bp fragment (basepairs 301 ∼ 1254) of the B. bronchiseptica aroA gene was replaced with an N-terminal, 930-bp fragment (basepairs 1–930; PMTN) or a C-terminal, 900-bp fragment (base pairs 2959 ∼ 3858; PMTC) of the PMT encoding gene toxA. The resulting strains, denoted as Bb-PMTN or Bb-PMTC, expressed PMTN and PMTC, as evidenced by ELISA using polyclonal against full-length of PMT. Phenotypical analyses revealed that Bb-PMTN and Bb-PMTC grew much slower than wild type strains in tryptic soy broth. These strains also displayed significantly decreased 161-fold-virulence compared to the wildtype strains in mouse models. Intranasal immunization of Bb-PMTN and Bb-PMTC in mice induced high levels of antibodies against B. bronchiseptica and PMT, as well as IFN-γ and IL-10 in mouse sera, and most importantly, high titers of sIgA in mouse lungs. Vaccination with these two engineering strains provided 100% protection of mice against lethal challenge with B. bronchiseptica and 80%∼100% protection against lethal challenge with PMT, with Bb-PMTN exhibiting 1.25-fold greater immunogenic efficacy over Bb-PMTC. This study highlights the use of B. bronchiseptica attenuated strains as live mucosal vectors to deliver heterologous antigens.

Original languageEnglish (US)
Pages (from-to)3771-3780
Number of pages10
JournalVaccine
Volume40
Issue number27
DOIs
StatePublished - Jun 15 2022

Keywords

  • B. bronchiseptica
  • Immunogenic efficacy
  • Pasteurella multocida toxin
  • Single-component mucosal vaccine
  • aroA-attenuation

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • General Immunology and Microbiology
  • Infectious Diseases
  • Molecular Medicine
  • General Veterinary

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