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dc.contributor.authorLie, Mengyao
dc.contributor.authorFeng, Wenchao
dc.contributor.authorZhu, Hui
dc.contributor.authorLei, Benfang
dc.date.accessioned2016-01-13T20:15:41Z
dc.date.available2016-01-13T20:15:41Z
dc.date.issued2015-04
dc.identifier.citationLiu, Mengyao, Wenchao Feng, Hui Zhu, and Benfang Lei. “A Neutralizing Monoclonal IgG1 Antibody of Platelet-Activating Factor Acetylhydrolase SsE Protects Mice Against Lethal Subcutaneous Group A Streptococcus Infection.” Edited by A. Camilli. Infection and Immunity 83, no. 7 (April 27, 2015): 2796–2805. doi:10.1128/iai.00073-15.en_US
dc.identifier.issn0019-9567
dc.identifier.urihttps://scholarworks.montana.edu/xmlui/handle/1/9486
dc.description.abstractGroup A Streptococcus (GAS) can cause life-threatening invasive infections, including necrotizing fasciitis. There are no effective treatments for severe invasive GAS infections. The platelet-activating factor (PAF) acetylhydrolase SsE produced by GAS is required for invasive GAS to evade innate immune responses and to invade soft tissues. This study determined whether the enzymatic activity of SsE is critical for its function in GAS skin invasion and inhibition of neutrophil recruitment and whether SsE is a viable target for immunotherapy for severe invasive GAS infections. An isogenic derivative of M1T1 strain MGAS5005 producing SsE with an S178A substitution (SsES178A), an enzymatically inactive SsE mutant protein, was generated. This strain induced higher levels of neutrophil infiltration and caused smaller lesions than MGAS5005 in subcutaneous infections of mice. This phenotype is similar to that of MGAS5005 sse deletion mutants, indicating that the enzymatic activity of SsE is critical for its function. An anti-SsE IgG1 monoclonal antibody (MAb), 2B11, neutralized the PAF acetylhydrolase activity of SsE. Passive immunization with 2B11 increased neutrophil infiltration, reduced skin invasion, and protected mice against MGAS5005 infection. However, 2B11 did not protect mice when it was administered after MGAS5005 inoculation. MGAS5005 induced vascular effusion at infection sites at early hours after GAS inoculation, suggesting that 2B11 did not always have access to infection sites. Thus, the enzymatic activity of SsE mediates its function, and SsE has the potential to be included in a vaccine but is not a therapeutic target. An effective MAb-based immunotherapy for severe invasive GAS infections may need to target virulence factors that are critical for systemic survival of GAS.en_US
dc.rightsCC BY 4.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleA Neutralizing Monoclonal IgG1 Antibody of Platelet-Activating Factor Acetylhydrolase SsE Protects Mice against Lethal Subcutaneous Group A StreptococcusInfectionen_US
dc.typeArticleen_US
mus.citation.extentfirstpage2796en_US
mus.citation.extentlastpage2805en_US
mus.citation.issue7en_US
mus.citation.journaltitleInfection and Immunityen_US
mus.citation.volume83en_US
mus.identifier.categoryHealth & Medical Sciencesen_US
mus.identifier.doi10.1128/iai.00073-15en_US
mus.relation.collegeCollege of Agricultureen_US
mus.relation.collegeCollege of Letters & Scienceen_US
mus.relation.departmentMicrobiology & Immunology.en_US
mus.relation.universityMontana State University - Bozemanen_US
mus.data.thumbpage7en_US


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