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Evaluation of Francisella tularensis Δ pdpC as a candidate live attenuated vaccine against respiratory challenge by a virulent SCHU P9 strain of Francisella tularensis in a C57BL/6J mouse model
Author(s) -
Tian Deyu,
Uda Akihiko,
Park Eunsil,
Hotta Akitoyo,
Fujita Osamu,
Yamada Akio,
Hirayama Kazuhiro,
Hotta Kozue,
Koyama Yuuki,
Azaki Mika,
Morikawa Shigeru
Publication year - 2018
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12555
Subject(s) - francisella tularensis , tularemia , biology , attenuated vaccine , francisella , virulence , microbiology and biotechnology , virology , immunization , immunology , immune system , gene , genetics
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.