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

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Abstract
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.