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Abstract
Tularemia is a severe infectious zoonotic disease caused by Francisella tularensis. Although F. tularensis is considered to be a potential biological weapon due to its high infectivity and mortality rate, no vaccine has been currently licensed. Recently, we reported that F. tularensis SCHU P9 derived ΔpdpC strain lacking the pathogenicity determinant protein C gene conferred stable and good protection in a mouse lethal model. In this study, the protective effect of ΔpdpC was evaluated using a monkey lethal model. Two cynomolgus macaques (Macaca fascicularis) intratracheally challenged with the virulent strain SCHU P9 were euthanized on 7 and 11 days post-challenge after the development of severe clinical signs. The bacterial replication in alveolar macrophages and type II epithelial cells in the lungs would cause severe pneumonia accompanied by necrosis. Conversely, two animals subcutaneously immunized with ΔpdpC survived 3 weeks after SCHU P9 challenge. Though one of the two animals developed mild symptoms of tularemia, bacterial replication was limited in the respiratory organs, which may be due to a high level of humoral and cellular immune responses against F. tularensis. These results suggest that the ΔpdpC mutant would be a safe and promising candidate as a live attenuated tularemia vaccine.
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Details
1 Laboratory of Veterinary Public Health, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan
2 Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan
3 Division of Experimental Animal Research, National Institute of Infectious Disease, Gakuen 4-7-1, Musashimurayama-shi, Tokyo, Japan
4 Department of Pathology, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan
5 Laboratory of Veterinary Public Health, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
6 Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan; Major Track of Applied Veterinary Science, Doctoral Course of the United Graduate School of Veterinary Sciences, Gifu University, Gifu-shi, Gifu, Japan
7 Department of Veterinary Science, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan; Department of Integrated Science in Physics and Biology, College of Humanities and Sciences, Nihon University, Setagaya-ku, Tokyo, Japan