Evaluation of Francisella tularensis ΔpdpC as a candidate live attenuated vaccine against respiratory challenge by a virulent SCHU P9 strain of Francisella tularensis in a C57BL/6J mouse model

• Deyu Tian

• Akihiko Uda

• Eun-sil Park

• Akitoyo Hotta

• Osamu Fujita

• Akio Yamada

• Kazuhiro Hirayama

• Kozue Hotta

• Yuuki Koyama

• Mika Azaki

• Shigeru Morikawa

抄録

<jats:label /> Francisella tularensis , which causes tularemia, is an intracellular gram‐negative bacterium. F. tularensis has received significant attention in recent decades because of its history as a biological weapon. Thus, development of novel vaccines against tularemia has been an important goal. The attenuated F. tularensis strain Δ pdpC , in which the pathogenicity determinant protein C gene ( pdpC ) has been disrupted by TargeTron mutagenesis, was investigated as a potential vaccine candidate for tularemia in the present study. C57BL/6J mice immunized s.c. with 1 × 10 6 CFUs of Δ pdpC were challenged intranasally with 100× the median lethal dose (LD 50 ) of a virulent SCHU P9 strain 21 days post immunization. Protection against this challenge was achieved in 38% of immunized C57BL/6J mice administered 100 LD 50 of this strain. Conversely, all unimmunized mice succumbed to death 6 days post challenge. Survival rates were significantly higher in vaccinated than in unimmunized mice. In addition, Δ pdpC was passaged serially in mice to confirm its stable attenuation. Low bacterial loads persisted in mouse spleens during the first to tenth passages. No statistically significant changes in the number of CFUs were observed during in vivo passage of Δ pdpC . The inserted intron sequences for disrupting pdpC were completely maintained even after the tenth passage in mice. Considering the stable attenuation and intron sequences, it is suggested that Δ pdpC is a promising tularemia vaccine candidate.

収録刊行物

• Microbiology and immunology / Japanese Society for Bacteriology, Japanese Society for Virology, Japanese Society for Host Defense Research

  Microbiology and immunology / Japanese Society for Bacteriology, Japanese Society for Virology, Japanese Society for Host Defense Research 62 (1), 24-33, 2018-01

  Richmond : Blackwell Publishing Asia Pty

キーワード

• ΔpdpC
• Francisella tularensis
• mouse
• vaccination

詳細情報

• CRID: 1520573330330759296
• NII論文ID: 40021443639
• NII書誌ID: AA00738350
• ISSN: 03855600
• ISSN: 13480421
• DOI: 10.1111/1348-0421.12555
• NDL書誌ID: 028781083
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028781083
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1348-0421.12555
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1111/1348-0421.12555
• Web Site: https://search.jamas.or.jp/link/ui/2019085564
• 本文言語コード: en
• NDL 雑誌分類:
  • ZS9(科学技術--医学--病理学・微生物学・寄生虫学・感染・免疫学・血清学・アレルギー)
• データソース種別:
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN