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Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague
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| Zeitschriftentitel: | Clinical and Vaccine Immunology |
|---|---|
| Personen und Körperschaften: | , |
| In: | Clinical and Vaccine Immunology, 16, 2009, 12, S. 1720-1727 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Eisele, Nicholas A. Anderson, Deborah M. Eisele, Nicholas A. Anderson, Deborah M. |
|---|---|
| author |
Eisele, Nicholas A. Anderson, Deborah M. |
| spellingShingle |
Eisele, Nicholas A. Anderson, Deborah M. Clinical and Vaccine Immunology Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague Microbiology (medical) Clinical Biochemistry Immunology Immunology and Allergy |
| author_sort |
eisele, nicholas a. |
| spelling |
Eisele, Nicholas A. Anderson, Deborah M. 1556-6811 1556-679X American Society for Microbiology Microbiology (medical) Clinical Biochemistry Immunology Immunology and Allergy http://dx.doi.org/10.1128/cvi.00333-09 <jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>Yersinia pestis</jats:italic> causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of <jats:italic>Y. pestis</jats:italic> by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens. </jats:p> Dual-Function Antibodies to <i>Yersinia pestis</i> LcrV Required for Pulmonary Clearance of Plague Clinical and Vaccine Immunology |
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| title |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_unstemmed |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_full |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_fullStr |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_full_unstemmed |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_short |
Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_sort |
dual-function antibodies to
<i>yersinia pestis</i>
lcrv required for pulmonary clearance of plague |
| topic |
Microbiology (medical) Clinical Biochemistry Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.1128/cvi.00333-09 |
| publishDate |
2009 |
| physical |
1720-1727 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>
<jats:italic>Yersinia pestis</jats:italic>
causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of
<jats:italic>Y. pestis</jats:italic>
by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens.
</jats:p> |
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| author | Eisele, Nicholas A., Anderson, Deborah M. |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>Yersinia pestis</jats:italic> causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of <jats:italic>Y. pestis</jats:italic> by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens. </jats:p> |
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| institution | DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1 |
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| spelling | Eisele, Nicholas A. Anderson, Deborah M. 1556-6811 1556-679X American Society for Microbiology Microbiology (medical) Clinical Biochemistry Immunology Immunology and Allergy http://dx.doi.org/10.1128/cvi.00333-09 <jats:title>ABSTRACT</jats:title> <jats:p> <jats:italic>Yersinia pestis</jats:italic> causes pneumonic plague, a necrotic pneumonia that rapidly progresses to death without early treatment. Antibodies to the protective antigen LcrV are thought to neutralize its essential function in the type III secretion system (TTSS) and by themselves are capable of inducing immunity to plague in mouse models. To develop multivalent LcrV antibodies as a therapeutic treatment option, we screened for monoclonal antibodies (MAbs) to LcrV that could prevent its function in the TTSS. Although we were able to identify single and combination MAbs that provided the high-level inhibition of the TTSS, these did not promote phagocytosis in vitro and were only weakly protective in a mouse pneumonic plague model. Only one MAb, BA5, was able to protect mice from pneumonic plague. In vitro, MAb BA5 blocked the TTSS with efficiency equal to or even less than that of other MAbs as single agents or as combinations, but its activity led to increased phagocytic uptake. Polyclonal anti-LcrV was superior to BA5 in promoting phagocytosis and also was more efficient in protecting mice from pneumonic plague. Taken together, the data support a hypothesis whereby the pulmonary clearance of <jats:italic>Y. pestis</jats:italic> by antibodies requires both the neutralization of the TTSS and the simultaneous stimulation of innate signaling pathways used by phagocytic cells to destroy pathogens. </jats:p> Dual-Function Antibodies to <i>Yersinia pestis</i> LcrV Required for Pulmonary Clearance of Plague Clinical and Vaccine Immunology |
| spellingShingle | Eisele, Nicholas A., Anderson, Deborah M., Clinical and Vaccine Immunology, Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague, Microbiology (medical), Clinical Biochemistry, Immunology, Immunology and Allergy |
| title | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_full | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_fullStr | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_full_unstemmed | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_short | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| title_sort | dual-function antibodies to <i>yersinia pestis</i> lcrv required for pulmonary clearance of plague |
| title_unstemmed | Dual-Function Antibodies to Yersinia pestis LcrV Required for Pulmonary Clearance of Plague |
| topic | Microbiology (medical), Clinical Biochemistry, Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.1128/cvi.00333-09 |