M. Achtman, K. Zurth, C. Morelli, G. Torrea, A. Guiyoule et al., 419 Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia 420 pseudotuberculosis, Proc. Natl. Acad. Sci. U.S.A, vol.96, pp.14043-14048, 1999.

J. M. Alonso, A. Joseph-francois, D. Mazigh, H. Bercovier, and H. H. Mollaret, Résistance à la peste de souris expérimentalement infectées par Yersinia 423 enterocolitica, Ann. Microbiol. (Inst Pasteur), vol.422, pp.203-207, 1978.

G. W. Anderson, D. G. Heath, C. R. Bolt, S. L. Welkos, and A. M. Friedlander, Short-and long-term efficacy of single-dose subunit vaccines against Yersinia 426 pestis in mice, Am. J. Trop. Med. Hyg, vol.425, pp.793-799, 1998.

G. P. Andrews, D. G. Heath, G. W. Anderson, S. L. Welkos, and A. M. Friedlander, Fraction 1 capsular antigen (F1) purification from Yersinia pestis CO92 and from 429 an Escherichia coli recombinant strain and efficacy against lethal plague challenge, vol.428, pp.2180-2187, 1996.

A. P. Anisimov, L. E. Lindler, and G. B. Pier, Intraspecific diversity of Yersinia 432 pestis, Clin Microbiol Rev, vol.17, pp.434-464, 2004.

S. S. Bubeck and P. H. Dube, Yersinia pestis CO92 delta yopH is a potent live, 434 attenuated plague vaccine, Clin Vaccine Immunol, vol.14, pp.1235-1238, 2007.

E. E. Cangiani, F. R. Guiraldi, S. E. Pinto, and B. M. De-medeiros, Kinetics of 436 B cell response during Yersinia enterocolitica infection in resistant and susceptible strains 437 of mice, Immunol Invest, vol.36, pp.387-402, 2007.

P. S. Chain, E. Carniel, F. W. Larimer, J. Lamerdin, P. O. Stoutland et al., , p.439

A. M. Georgescu, L. M. Vergez, M. L. Land, V. L. Motin, R. R. Brubaker et al.,

D. Souza, J. M. Dacheux, A. Elliott, L. J. Derbise, E. Hauser et al., 442 Insights into the evolution of Yersinia pestis through whole-genome comparison with 443 Yersinia pseudotuberculosis, Proc. Natl. Acad. Sci. U.S.A, vol.101, pp.13826-13831, 2004.

F. Collyn, A. Billault, C. Mullet, M. Simonet, and M. Marceau, YAPI, a new 445 Yersinia pseudotuberculosis pathogenicity island, Infect Immun, vol.72, p.10, 2004.

F. Collyn, M. A. Lety, S. Nair, V. Escuyer, A. B. Younes et al.,

. Marceau, Yersinia pseudotuberculosis harbors a type IV pilus gene cluster that 448 contributes to pathogenicity, Infect. Immun, vol.70, p.11, 2002.

B. Corthesy, H. R. Gaskins, and A. Mercenier, Cross-talk between probiotic 450 bacteria and the host immune system, J Nutr, vol.137, p.12, 2007.

A. M. De-almeida, A. Guiyoule, I. Guilvout, I. Iteman, G. Baranton et al., Chromosomal irp2 gene in Yersinia : distribution, expression, deletion and impact 453 on virulence, Microb. Pathog, vol.452, p.13, 1993.

F. D. Finkelman, J. Holmes, I. M. Katona, J. F. Urban, M. P. Beckmann et al.,

K. A. Park, R. L. Schooley, T. R. Coffman, W. E. Mosmann, and . Paul, , 1990.

, Lymphokine control of in vivo immunoglobulin isotype selection, Annu Rev Immunol, vol.457, p.14

Y. Flashner, E. Mamroud, A. Tidhar, R. Ber, M. Aftalion et al., Generation, vol.460, p.24, 2004.

, Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel 25

P. C. Oyston, E. D. Williamson, S. E. Leary, S. M. Eley, K. F. Griffin et al.,

W. , Immunization with live recombinant Salmonella typhimurium aroA 505 producing F1 antigen protects against plague, Infect. Immun, vol.63, p.30, 1995.

J. Parkhill, B. W. Wren, N. R. Thomson, and R. W. Titball, , p.507

M. Prentice, K. D. Sebaihia, C. James, K. L. Churcher, S. Mungall et al.,

S. D. Basham, K. Bentley, A. M. Brooks, T. Cerdeno-tarraga, and A. Chillingworth,

R. M. Cronin, P. Davies, G. Davis, T. Dougan, N. Feltwell et al.,

A. V. Jagels and . Karlyshev, Genome sequence of Yersinia pestis, the 511 causative agent of plague, Nature, vol.413, p.31, 2001.

A. V. Philipovskiy and S. T. Smiley, Vaccination with live Yersinia pestis 513 primes CD4 and CD8 T cells that synergistically protect against lethal pulmonary Y. 514 pestis infection, Infect Immun, vol.75, p.32, 2007.

C. Pilette, Y. Ouadrhiri, V. Godding, J. P. Vaerman, and Y. Sibille, Lung 516 mucosal immunity: immunoglobulin-A revisited, Eur Respir J, vol.18, p.33, 2001.

F. Pouillot, A. Derbise, M. Kukkonen, J. Foulon, T. K. Korhonen et al., Evaluation of O-antigen inactivation on Pla activity and virulence of Yersinia 519 pseudotuberculosis harbouring the pPla plasmid, Microbiology, vol.518, p.34, 2005.

M. Ratsitorahina, S. Chanteau, L. Rahalison, L. Ratsifasoamanana, and P. Boisier, Epidemiological and diagnostic aspects of the outbreak of pneumonic plague in 522 Madagascar, Lancet, vol.521, p.35, 2000.

A. Roggenkamp, A. M. Geiger, L. Leitritz, A. Kessler, and J. Heesemann, 524 Passive immunity to infection with Yersinia spp. mediated by anti-recombinant V antigen 525 is dependent on polymorphism of V antigen, Infect Immun, vol.65, p.36, 1997.

M. Simonet, P. Berche, D. Mazigh, and M. Veron, Protection against Yersinia 527 infection induced by non-virulence-plasmid-encoded antigens, J. Med. Microbiol, vol.20, p.37, 1985.

W. J. Simpson, R. E. Thomas, and T. G. Schwan, Recombinant Capsular 530, 1990.

. Antigen, Fraction-1) from Yersinia pestis Induces a Protective Antibody Response in 531 BALB/c Mice, Am. J. Trop. Med. Hyg, vol.43, p.38

S. T. Smiley, Current challenges in the development of vaccines for pneumonic 533 plague, Expert Rev Vaccines, vol.7, p.39, 2008.

D. B. Smith and K. S. Johnson, Single-step purification of polypeptides 535 expressed in Escherichia coli as fusions with glutathione S-transferase, Gene, vol.67, p.40, 1988.

V. L. Taylor, R. W. Titball, and P. C. Oyston, Oral immunization with a dam 537 mutant of Yersinia pseudotuberculosis protects against plague, Microbiology-Sgm, vol.538, p.41, 2005.

T. Une and R. R. Brubaker, Morita, and M. Wake. 1978. Mechanisms of long and short term 542 immunity to plague, Immunology, vol.133, p.43, 1984.

T. J. Welch, W. F. Fricke, P. F. Mcdermott, D. G. White, M. L. Rosso et al., , p.544

M. K. Mammel, M. Eppinger, M. J. Rosovitz, D. Wagner, L. Rahalison et al.,

J. M. Leclerc, L. E. Hinshaw, T. A. Lindler, E. Cebula, J. Carniel et al., , 2007.

, Multiple antimicrobial resistance in plague: an emerging public health risk, PLoS ONE, vol.547, issue.2, p.309

S. L. Welkos, K. M. Davis, L. M. Pitt, P. L. Worsham, and A. M. Freidlander, 549 Studies on the contribution of the F1 capsule-associated plasmid pFra to the virulence of 550 Yersinia pestis, Contrib Microbiol Immunol, vol.13, p.47, 1995.

E. D. Williamson, S. M. Eley, K. F. Griffin, M. Green, P. Russell et al.,

C. F. Oyston, T. Easterbrook, K. M. Reddin, A. Robinson, and R. W. Titball, 556 A new improved sub-unit vaccine for plague: The basis of protection, FEMS Immunol, 1995.

, Med. Microbiol, vol.12, pp.223-230

E. D. Williamson, H. C. Flick-smith, C. Lebutt, C. A. Rowland, S. M. Jones et al.,

R. J. Waters, J. Gwyther, P. J. Miller, M. Packer, and . Irving, Human immune 560 response to a plague vaccine comprising recombinant F1 and V antigens, Infect. Immun, vol.561, pp.3598-3608, 1960.

, Bull Wld Hlth Org, vol.23, p.50

Y. Zhang and J. B. Bliska, Role of macrophage apoptosis in the pathogenesis of 566 Yersinia, Curr Top Microbiol Immunol, vol.289, p.51, 2005.

D. Zhou, Y. Han, E. Dai, Y. Song, D. Pei et al.,

Y. , Defining the genome content of live plague vaccines by use of whole-569 genome DNA microarray, Vaccine, vol.22, pp.3367-3374, 2004.

, A: Groups of 8 mice received either saline (unvaccinated), 1 sc inoculation of 10 7 cfu of EV76 614 (positive control group), or 1 or 2 ig inoculations of 2x10 9 cfu of IP32680 at a 30 day interval

, All mice were challenged sc with a lethal dose of 10 3 cfu of Y. pestis CO92 at d30 (mice with 616 EV76 or IP32680 given once) or d60 (mice with IP32680 given twice) and mortality was 617 followed thereafter daily for 3 weeks

, B: Enumeration of CO92 bacteria in organs of challenged mice. Organs and blood from 620 unvaccinated mice and from mice having received the IP32680 strain twice were taken to 621 determine the bacterial load two days after a Y. pestis challenge performed as in A. Given are 622 the cfu per g (liver), or per whole organ (spleen, 2 inguinal lymph nodes) or per ml of blood

, Results from 2 independant experiments were pooled and shown are the means of Log cfu ± 624 SEM of a total of 16 vaccinated mice and 21 unvaccinated mice. ND: not detected, p.625