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Infection and Immunity, December 2008, p. 5588-5597, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00699-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immunization with Recombinant V10 Protects Cynomolgus Macaques from Lethal Pneumonic Plague{triangledown}

Claire A. Cornelius,1 Lauriane E. Quenee,1 Katie A. Overheim,2 Frederick Koster,2 Trevor L. Brasel,2 Derek Elli,1 Nancy A. Ciletti,1 and Olaf Schneewind1*

Department of Microbiology, University of Chicago, Chicago, Illinois,1 Lovelace Biomedical and Environmental Research Institute (LBERI), Albuquerque, New Mexico2

Received 3 June 2008/ Returned for modification 2 July 2008/ Accepted 3 September 2008

Vaccine and therapeutic strategies that prevent infections with Yersinia pestis have been sought for over a century. Immunization with live attenuated (nonpigmented) strains and immunization with subunit vaccines containing recombinant low-calcium-response V antigen (rLcrV) and recombinant F1 (rF1) antigens are considered effective in animal models. Current antiplague subunit vaccines in development for utilization in humans contain both antigens, either as equal concentrations of the two components (rF1 plus rLcrV) or as a fusion protein (rF1-rLcrV). Here, we show that immunization with either purified rLcrV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis. In addition, passive immunization studies showed that specific antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection against bubonic plague challenge in mice. Finally, we found that when we compared the reactivities of anti-rLcrV and anti-rV10 immune sera from cynomolgus macaques, BALB/c mice, and brown Norway rats with LcrV-derived peptides, rV10, but not rLcrV immune sera, lacked antibodies recognizing linear LcrV oligopeptides.

* Corresponding author: Mailing address: Department of Microbiology, 920 East 58th Street, Chicago, IL 60637. Phone: (773) 843-9060. Fax: (773) 834-8150. E-mail: oschnee{at}bsd.uchicago.edu

{triangledown} Published ahead of print on 15 September 2008.

Editor: J. B. Bliska

Infection and Immunity, December 2008, p. 5588-5597, Vol. 76, No. 12
0019-9567/08/$08.00+0     doi:10.1128/IAI.00699-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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