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Infection and Immunity, August 2008, p. 3808-3816, Vol. 76, No. 8
0019-9567/08/$08.00+0     doi:10.1128/IAI.00034-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Oral Vaccination against Bubonic Plague Using a Live Avirulent Yersinia pseudotuberculosis Strain

Thierry Blisnick,^1, Patrick Ave,² Michel Huerre,² Elisabeth Carniel,¹ and Christian E. Demeure^1*

Yersinia Research Unit,¹ Histotechnology and Pathology Research and Expertise Unit, Institut Pasteur, Paris, France²

Received 10 January 2008/ Returned for modification 12 February 2008/ Accepted 21 May 2008

We evaluated the possibility of using Yersinia pseudotuberculosis as a live vaccine against plague because it shares high genetic identity with Y. pestis while being much less virulent, genetically much more stable, and deliverable orally. A total of 41 Y. pseudotuberculosis strains were screened by PCR for the absence of the high pathogenicity island, the superantigens YPM, and the type IV pilus and the presence of the pYV virulence plasmid. One strain (IP32680) fulfilled these criteria. This strain was avirulent in mice upon intragastric or subcutaneous inoculation and persisted for 2 months in the mouse intestine without clinical signs of disease. IP32680 reached the mesenteric lymph nodes, spleen, and liver without causing major histological lesions and was cleared after 13 days. The antibodies produced in vaccinated animals recognized both Y. pseudotuberculosis and Y. pestis antigens efficiently. After a subcutaneous challenge with Y. pestis CO92, bacteria were found in low amounts in the organs and rarely in the blood of vaccinated animals. One oral IP32680 inoculation protected 75% of the mice, and two inoculations induced much higher antibody titers and protected 88% of the mice. Our results thus validate the concept that an attenuated Y. pseudotuberculosis strain can be an efficient, inexpensive, safe, and easy-to-produce live vaccine for oral immunization against bubonic plague.

Published ahead of print on 27 May 2008.

Editor: J. B. Bliska

Present address: Unité Postulante de Biologie Cellulaire des Trypanosomes, Institut Pasteur, Paris, France.