title: Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Cornelius
authors.forename: Lauriane E
authors.initials: LE
authors.lastname: Quenee
authors.forename: Katie A
authors.initials: KA
authors.lastname: Overheim
authors.forename: Frederick
authors.initials: F
authors.lastname: Koster
authors.forename: Trevor L
authors.initials: TL
authors.lastname: Brasel
authors.forename: Derek
authors.initials: D
authors.lastname: Elli
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Ciletti
authors.forename: Olaf
authors.initials: O
authors.lastname: Schneewind
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008168:Lung / Q000276:immunology / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008992:Monkey Diseases / Q000276:immunology / Q000517:prevention & control; D010930:Plague / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D015010:Yersinia pestis
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C086725:caf1 protein, Yersinia pestis
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