IAI Accepts, published online ahead of print on 15 September 2008

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Infect. Immun. doi:10.1128/IAI.00699-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immunization with recombinant V10 protects Cynomolgus macaques from lethal pneumonic plague

Claire A. Cornelius, Lauriane E. Quenee, Katie A. Overheim, Frederick Koster, Trevor L. Brasel, Derek Elli, Nancy A. Ciletti, and Olaf Schneewind^*

Department of Microbiology, University of Chicago, Chicago, Illinois; and Lovelace Biomedical and Environmental Research Institute (LBERI), Albuquerque, New Mexico

^* To whom correspondence should be addressed. Email: oschnee{at}bsd.uchicago.edu.

Vaccine and therapeutic strategies that prevent infections with Yersinia pestis have been sought for over a century. Immunization with live-attenuated (non-pigmented) strains or subunit vaccines with recombinant LcrV or F1 antigens are considered effective in animal models. Current anti-plague subunit vaccines in development for human utilization incorporate both antigens either as an equal concentration of components (rF1 + rLcrV) or as a fusion protein (rF1-LcrV). Here, we show that immunization with either purified rLcrV (a protein at the tip of type III needles) or its variant rV10 (lacking amino acid residues 271-300) alone or in combination with rF1 prevented pneumonic lesions and disease pathogenesis. In addition, passive immunization studies show that specific antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, confer protection against bubonic plague challenge in mice. Finally, we show that when comparing anti-rLcrV and rV10 immune sera from Cynomolgus macaques, BALB/c mice and Brown Norway rats for reactivity with LcrV derived peptides, rV10, but not rLcrV immune sera, lacked antibodies recognizing linear LcrV oligopeptides.

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