Synergistic Protection of Mice against Plague with Monoclonal Antibodies Specific for the F1 and V Antigens of
            <i>Yersinia pestis</i>

Hill, Jim; Copse, Catherine; Leary, Sophie E.C.; Stagg, Anthony J.; Williamson, E. Diane; Titball, Richard W.

doi:10.1128/iai.71.4.2234-2238.2003

Cited by 95 publications

(69 citation statements)

References 45 publications

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“…LcrV in Yersinia is part of the translocation apparatus and is required to deliver antihost effector proteins into host cells and, like PcrV in P. aeruginosa, is also essential for translocation of the cytotoxins. Antibodies directed against PcrV (39) and LcrV (20,21) protect animals against infections, which has implicated these immunogens as possible candidates for vaccine therapy.…”

Section: Discussionmentioning

confidence: 99%

Early Immune Response to the Components of the Type III System of Pseudomonas aeruginosa in Children with Cystic Fibrosis

et al. 2005

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The lungs of patients with cystic fibrosis (CF) are colonized initially by Pseudomonas aeruginosa, which is associated with progressive lung destruction and increased mortality. The pathogenicity of P. aeruginosa is caused by a number of virulence factors, including exotoxin A (ETA) and the type III cytotoxins (ExoS, ExoT, ExoU, and ExoY). P. aeruginosa contacts the plasma membrane to deliver type III cytotoxins through a channel formed by PopB, PopD, and PcrV; ETA enters mammalian cells via receptor-mediated endocytosis. The Wisconsin CF Neonatal Screening Project is a longitudinal investigation to assess the potential benefits and risks of newborn screening for CF; the project was the source of serum samples used in this study. Past studies evaluated the longitudinal appearance of antibodies to ETA and elastase and P. aeruginosa infections in patients with CF. The current study characterized the longitudinal appearance of antibodies to components of the type III system in children with CF. Western blot analyses showed that serum antibodies to PopB, PcrV, and ExoS were common. Longitudinal enzyme-linked immunosorbent assays determined that the first detection of antibodies to pooled ExoS/PopB occurred at a time similar to those of detection of antibodies to a P. aeruginosa cell lysate and the identification of oropharyngeal cultures positive for P. aeruginosa. This indicates that children with CF are colonized early with P. aeruginosa expressing the type III system, implicating it in early pathogenesis, and implies that surveillance of clinical symptoms, oropharyngeal cultures, and seroconversion to type III antigens may facilitate early detection of P. aeruginosa infections.

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Section: Discussionmentioning

confidence: 99%

Early Immune Response to the Components of the Type III System of Pseudomonas aeruginosa in Children with Cystic Fibrosis

et al. 2005

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“…Plague still remains a serious public health threat in some regions of the world, accounts for the deaths of 200 million people throughout recorded history, and is endemic to Africa, India, and the southwestern states of the United States (1,3). Because plague is highly infectious and can readily spread by aerosolization, it poses as a bioterrorist threat (4).…”

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confidence: 99%

“…Elevated anti-F1 Ab titers have been correlated with animal survival following plague infection (11). Virulence Ag (V-Ag) 3 is a 37-kDa protein encoded by the lcrV gene on the conserved plasmid pCD1 and plays a multifunctional role in Y. pestis virulence. V-Ag serves as a positive regulator for expression of low calcium response virulence genes (12) and is involved in the translocation of effector proteins into eukaryotic cells via the type III secretion system (13,14).…”

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confidence: 99%

Oral Vaccination withSalmonellaSimultaneously ExpressingYersinia pestisF1 and V Antigens Protects against Bubonic and Pneumonic Plague

Yang

Hinnebusch

Trunkle

et al. 2007

The Journal of Immunology

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The gut provides a large area for immunization enabling the development of mucosal and systemic Ab responses. To test whether the protective Ags to Yersinia pestis can be orally delivered, the Y. pestis caf1 operon, encoding the F1-Ag and virulence Ag (V-Ag) were cloned into attenuated Salmonella vaccine vectors. F1-Ag expression was controlled under a promoter from the caf1 operon; two different promoters (P), PtetA in pV3, PphoP in pV4, as well as a chimera of the two in pV55 were tested. F1-Ag was amply expressed; the chimera in the pV55 showed the best V-Ag expression. Oral immunization with Salmonella-F1 elicited elevated secretory (S)-IgA and serum IgG titers, and Salmonella-V-Ag(pV55) elicited much greater S-IgA and serum IgG Ab titers than Salmonella-V-Ag(pV3) or Salmonella-V-Ag(pV4). Hence, a new Salmonella vaccine, Salmonella-(F1+V)Ags, made with a single plasmid containing the caf1 operon and the chimeric promoter for V-Ag allowed the simultaneous expression of F1 capsule and V-Ag. Salmonella-(F1+V)Ags elicited elevated Ab titers similar to their monotypic derivatives. For bubonic plague, mice dosed with Salmonella-(F1+V)Ags and Salmonella-F1-Ag showed similar efficacy (>83% survival) against ∼1000 LD50 Y. pestis. For pneumonic plague, immunized mice required immunity to both F1- and V-Ags because the mice vaccinated with Salmonella-(F1+V)Ags protected against 100 LD50 Y. pestis. These results show that a single Salmonella vaccine can deliver both F1- and V-Ags to effect both systemic and mucosal immune protection against Y. pestis.

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“…A PenCentuary (PenCentuary, Inc., PA) intratracheal microsprayer device was used to deliver MAbs 7.3 and F1-04-A-G1 in a 50-l volume of phosphate-buffered saline (PBS) (3). Protective plague MAbs F1-04-A-G1 (1) and 7.3 (12) were affinity purified from tissue culture cell supernatants as described previously (11). Each mouse was dosed with 77.5 g of each antibody.…”

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confidence: 99%

Administration of Antibody to the Lung Protects Mice against Pneumonic Plague

et al. 2006

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Synergistic Protection of Mice against Plague with Monoclonal Antibodies Specific for the F1 and V Antigens of Yersinia pestis

Cited by 95 publications

References 45 publications

Early Immune Response to the Components of the Type III System of Pseudomonas aeruginosa in Children with Cystic Fibrosis

Early Immune Response to the Components of the Type III System of Pseudomonas aeruginosa in Children with Cystic Fibrosis

Oral Vaccination withSalmonellaSimultaneously ExpressingYersinia pestisF1 and V Antigens Protects against Bubonic and Pneumonic Plague

Administration of Antibody to the Lung Protects Mice against Pneumonic Plague

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