Abstract
BackgroundPlague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined.Methodology and Principal FindingsThe sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis.Conclusions and SignificanceThe encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.
Highlights
Plague, the dreadful infectious disease that caused three major pandemics in history, is still a public health problem
An additional cause of concern is the recent identification in Madagascar of two Y. pestis strains naturally resistant to antibiotics, one of which was resistant to eight different antibiotics, including those recommended for plague treatment and prophylaxis [7]
We have developed a genetically defined Y. pseudotuberculosis strain strongly attenuated by deletion of virulence factors genes, which was induced to produce the Y. pestis F1 pseudocapsule
Summary
The dreadful infectious disease that caused three major pandemics in history, is still a public health problem. Human-to-human transmission of pneumonic plague favors a rapid spread of the disease in heavily populated areas, as occurred for example recently in Madagascar and in the Democratic Republic of Congo [5,6]. Antibiotherapy is currently the main tool to fight the disease, the residual plague mortality in endemic countries remains around 10% or more. This is mainly due to the difficulty for patients from areas far from health structures to receive the treatment on time. An additional cause of concern is the recent identification in Madagascar of two Y. pestis strains naturally resistant to antibiotics, one of which was resistant to eight different antibiotics, including those recommended for plague treatment and prophylaxis [7]. The strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
