title: Evaluation of protective potential of Yersinia pestis outer membrane protein antigens as possible candidates for a new-generation recombinant plague vaccine.
abstract: Plague caused by Yersinia pestis manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of Y. pestis represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against Y. pestis F1(-) strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT) Y. pestis CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from Escherichia coli for immunization purposes before challenging mice and rats with either the F1(-) mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1(-) CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of Y. pestis outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of Y. pestis strains.
authors.affiliation: Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Tatiana E
authors.initials: TE
authors.lastname: Erova
authors.forename: Jason A
authors.initials: JA
authors.lastname: Rosenzweig
authors.forename: Jian
authors.initials: J
authors.lastname: Sha
authors.forename: Giovanni
authors.initials: G
authors.lastname: Suarez
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Sierra
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Kirtley
authors.forename: Christina J
authors.initials: CJ
authors.lastname: van Lier
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Telepnev
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Motin
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Chopra
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D007106:Immune Sera; D007114:Immunization; D007116:Immunization, Passive; D064704:Levofloxacin; D051379:Mice; D015242:Ofloxacin / Q000627:therapeutic use; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D010931:Plague Vaccine / Q000276:immunology* / Q000627:therapeutic use; D010960:Plasminogen Activators / Q000235:genetics / Q000276:immunology; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology; D015010:Yersinia pestis / Q000235:genetics / Q000276:immunology*
chemical_list: C526543:Ail protein, Yersinia pestis; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D007106:Immune Sera; D010931:Plague Vaccine; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D037521:Virulence Factors; C086725:caf1 protein, Yersinia pestis; D064704:Levofloxacin; D015242:Ofloxacin; C078140:Pla protease, Yersinia pestis; D010960:Plasminogen Activators