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Infection and Immunity, February 2007, p. 878-885, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01529-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vaccination with Live Yersinia pestis Primes CD4 and CD8 T Cells That Synergistically Protect against Lethal Pulmonary Y. pestis Infection{triangledown}

Alexander V. Philipovskiy and Stephen T. Smiley*

Trudeau Institute, Saranac Lake, New York 12983

Received 22 September 2006/ Returned for modification 1 November 2006/ Accepted 13 November 2006

Vaccination with live attenuated Yersinia pestis confers protection against pneumonic plague but is not considered safe for general use. Subunit plague vaccines containing the Y. pestis F1 and LcrV proteins prime robust antibody responses but may not provide sufficient protection. To aid the development of a safe and effective plague vaccine, we are investigating roles for T cells during defense against Y. pestis infection. Here we demonstrate that vaccination of mice with live Y. pestis primes specific CD4 and CD8 T cells that, upon purification and direct transfer to naïve mice, synergistically protect against lethal intranasal Y. pestis challenge. While not preventing extrapulmonary dissemination, the coadministered T cells promote bacterial clearance and reduce bacteremia. These observations strongly suggest that development of pneumonic plague vaccines should strive to prime both CD4 and CD8 T cells. Finally, we demonstrate that vaccination with live Y. pestis primes CD4 and CD8 T cells that respond to Y. pestis strains lacking the capacity to express F1, LcrV, and all pCD1/pPCP-encoded proteins, suggesting that protective T cells likely recognize antigens distinct from those previously defined as targets for humoral immunity.

* Corresponding author. Mailing address: Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983. Phone: (518) 891-3080. Fax: (518) 891-5126. E-mail: ssmiley{at}trudeauinstitute.org.

{triangledown} Published ahead of print on 21 November 2006.

Editor: D. L. Burns

Infection and Immunity, February 2007, p. 878-885, Vol. 75, No. 2
0019-9567/07/$08.00+0     doi:10.1128/IAI.01529-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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