V antigen ofYersinia pestisinhibits neutrophil chemotaxis

Welkos, Susan L.; Friedlander, Arthur M.; McDowell, David A.; Weeks, Jenni Nichole; Tobery, Steven A.

doi:10.1006/mpat.1997.0188

Cited by 60 publications

(45 citation statements)

References 30 publications

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“…Y. pseudotuberculosis strain YpIII(pIB19:pTrcV) (Y. pseudotuberculosis pTrcV) has an in-frame deletion mutation of the plasmid pLcr-encoded lcrV gene and is transformed with the recombinant pTrcV expression plasmid (38). Polyclonal anti-V IgG was purified by protein A-Sepharose chromatography from the sera of rabbits vaccinated with purified His-tagged recombinant Y. pestis V (rV) (49). MAbs to rV were IgG purified from hybridoma culture supernatants and assessed for binding of rV by ELISA.…”

Section: Methodsmentioning

confidence: 99%

Development of In Vitro Correlate Assays of Immunity to Infection withYersinia pestis

Bashaw

Norris

Weeks

et al. 2007

Clin Vaccine Immunol

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Pneumonic plague is a severe, rapidly progressing disease for which there is no effective vaccine. Since the efficacy of new vaccines cannot be tested in humans, it is essential to develop in vitro surrogate assays that are valid predictors of immunity. The F1 capsule antigen stimulates a protective immune response to most strains of Yersinia pestis. However, strains of Y. pestis that are F1؊ but still virulent have been isolated, and an in vitro assay, the results which can predict protection against both F1؉ and F1 ؊ strains, is needed. The virulence antigen (V) is an essential virulence factor of Y. pestis and stimulates protective antibodies. We investigated potential correlates of plague immunity that are based on anti-V antibodymediated neutralization of Yersinia-induced macrophage cytotoxicity. The neutralizing activity of sera from mice vaccinated with an F1-V fusion candidate vaccine was determined. The decrease in the level of the apoptosis-specific enzyme caspase-3 significantly predicted survival in one-and two-dose vaccination experiments. Sera from F1-V-vaccinated nonhuman primates were evaluated with macrophage assays based on caspase-3 and on other markers manifested at the different stages in cell death. Using murineand human-derived macrophages in microscopic and fluorescence-activated-cell-sorting-based live/dead staining assays of terminal necrosis, we demonstrated a strong association between in vitro neutralization of macrophage cytotoxicity induced by serum-treated Yersinia and in vivo protection against lethal infection. These results provide a strong base for the development of reliable in vitro correlate bioassays that are predictive of protective immunity to plague.Pneumonic plague is a severe and rapidly progressing disease for which no fully effective vaccine exists. There is no licensed vaccine available that elicits complete immunity in animal models to pneumonic plague. Although the previously licensed vaccine for plague protected experimental animals against parenteral challenge, it was ineffective against pneumonic challenge (19, 27; M. L. Pitt, unpublished data). Furthermore, the former vaccine, which consisted of killed whole cells of virulent Yersinia pestis (27), did not protect against virulent nonencapsulated (F1 Ϫ ) strains (19) since the vaccine did not contain immunogenic quantities of the virulence antigen (V) or other potentially protective immunogens (8,9,21). It was previously demonstrated that a combination of both F1 capsular protein antigen and V effectively protects against both encapsulated (F1 ϩ ) and nonencapsulated (F1 Ϫ ) strains of Y. pestis (3). New candidate plague vaccines containing a single recombinant F1-V fusion protein or a combination of these two proteins have been developed (19, 49a).The protective efficacy against lethal challenge of these new candidate plague vaccines cannot be ethically tested in humans. Thus, it is essential that an in vitro surrogate marker that can reliably predict the level of protective immunity in sera from vaccinated i...

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Section: Methodsmentioning

confidence: 99%

Development of In Vitro Correlate Assays of Immunity to Infection withYersinia pestis

Bashaw

Norris

Weeks

et al. 2007

Clin Vaccine Immunol

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“…This occurs together with the degradation of pathogens within the phagosome and the presentation of pathogen antigens to the major histocompatibility complex (MHC) molecules. In this way the DCs can activate T cells by an MHC-specific manner [50]. In addition to the control of the costimulatory pathway, DCs seem to contribute to T-cell activation by overcoming the suppression of regulatory T cells (CD4 and CD8) by secretion of IL-6 [51].…”

Section: Interfering With the Antigen Presentation Of Dcsmentioning

confidence: 99%

“…The protective efficiencies for 24 of them were preliminarily evaluated using a mouse plague model. In addition to LcrV, nine proteins (YPO0606, YPO1914, YPO0612, YPO3119, YPO3047, YPO1377, YPCD1.05c, YPO0420, and YPO3720) may provide partial protection against challenge with a low dose (20 times the 50% lethal dose (20x LD [50]) of Y. pestis, but only YPO0606 could partially protect mice from infection with Y. pestis at a higher challenge dosage (200x LD [50]). These proteins would be the potential components for Y. pestis vaccine development.…”

Section: Strategies For Efficient Y Pestis Vaccinationmentioning

confidence: 99%

Role of immune response in Yersinia pestis infection

Amedei

Niccolai

Marino

et al. 2011

J Infect Dev Ctries

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Yersinia pestis (Y. Pestis) is an infamous pathogen causing plague pandemics throughout history and is a selected agent of bioterrorism threatening public health. Y. pestis was first isolated by Alexandre Yersin in 1894 in Hong Kong and in the following years from all continents. Plague is enzootic in different rodents and their fleas in Africa, North and South America, and Asia, including the Middle/Far East and ex-USSR countries. Comprehending the multifaceted interaction between Y. pestis and the host immune system will enable us to design more effective vaccines. Innate immune response and both components (humoral and cellular) of adaptive immune response contribute to host defense against Y. pestis infection, but the bacterium possesses different mechanisms to counteract the immune response. The review aims to analyze the role of immune response versus Yersinia pestis infection and to highlight the various stratagems adopted by Y. pestis to escape the immunological defenses.

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“…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). In addition, it has been suggested that V-Ag can act as an immunosuppressive agent, alter host cytokine production (15), and inhibit neutrophil chemotaxis (16). Based on these observations, perhaps the protective effect of anti-V-Ag Abs is due to their ability to neutralize V-Aginduced immunosuppression (17).…”

mentioning

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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V antigen ofYersinia pestisinhibits neutrophil chemotaxis

Cited by 60 publications

References 30 publications

Development of In Vitro Correlate Assays of Immunity to Infection withYersinia pestis

Development of In Vitro Correlate Assays of Immunity to Infection withYersinia pestis

Role of immune response in Yersinia pestis infection

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

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