Flagella hook protein FlgE is a novel vaccine candidate of
Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and h...
Ausführliche Beschreibung
Autor*in: |
Wan, Chuang [verfasserIn] Gao, Chen [verfasserIn] Xie, Qin [verfasserIn] Wang, Yin [verfasserIn] Cheng, Xin [verfasserIn] Fang, Yao [verfasserIn] Liu, Zhiyong [verfasserIn] Zhang, Weijun [verfasserIn] Zou, Quanming [verfasserIn] Lu, Guangwen [verfasserIn] Gu, Jiang [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2021 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: Vaccine - Amsterdam : Elsevier, 1983, 39, Seite 2386-2395 |
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Übergeordnetes Werk: |
volume:39 ; pages:2386-2395 |
DOI / URN: |
10.1016/j.vaccine.2021.03.051 |
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Katalog-ID: |
ELV005819954 |
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520 | |a Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. | ||
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700 | 1 | |a Gu, Jiang |e verfasserin |4 aut | |
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10.1016/j.vaccine.2021.03.051 doi (DE-627)ELV005819954 (ELSEVIER)S0264-410X(21)00344-3 DE-627 ger DE-627 rda eng 610 DE-600 44.45 bkl Wan, Chuang verfasserin aut Flagella hook protein FlgE is a novel vaccine candidate of 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. Genomic library Antigen screening FlgE Pneumonia Gao, Chen verfasserin aut Xie, Qin verfasserin aut Wang, Yin verfasserin aut Cheng, Xin verfasserin aut Fang, Yao verfasserin aut Liu, Zhiyong verfasserin aut Zhang, Weijun verfasserin aut Zou, Quanming verfasserin aut Lu, Guangwen verfasserin (orcid)0000-0001-7568-592X aut Gu, Jiang verfasserin aut Enthalten in Vaccine Amsterdam : Elsevier, 1983 39, Seite 2386-2395 Online-Ressource (DE-627)266886078 (DE-600)1468474-3 (DE-576)075961857 1873-2518 nnns volume:39 pages:2386-2395 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.45 Immunologie AR 39 2386-2395 |
spelling |
10.1016/j.vaccine.2021.03.051 doi (DE-627)ELV005819954 (ELSEVIER)S0264-410X(21)00344-3 DE-627 ger DE-627 rda eng 610 DE-600 44.45 bkl Wan, Chuang verfasserin aut Flagella hook protein FlgE is a novel vaccine candidate of 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. Genomic library Antigen screening FlgE Pneumonia Gao, Chen verfasserin aut Xie, Qin verfasserin aut Wang, Yin verfasserin aut Cheng, Xin verfasserin aut Fang, Yao verfasserin aut Liu, Zhiyong verfasserin aut Zhang, Weijun verfasserin aut Zou, Quanming verfasserin aut Lu, Guangwen verfasserin (orcid)0000-0001-7568-592X aut Gu, Jiang verfasserin aut Enthalten in Vaccine Amsterdam : Elsevier, 1983 39, Seite 2386-2395 Online-Ressource (DE-627)266886078 (DE-600)1468474-3 (DE-576)075961857 1873-2518 nnns volume:39 pages:2386-2395 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.45 Immunologie AR 39 2386-2395 |
allfields_unstemmed |
10.1016/j.vaccine.2021.03.051 doi (DE-627)ELV005819954 (ELSEVIER)S0264-410X(21)00344-3 DE-627 ger DE-627 rda eng 610 DE-600 44.45 bkl Wan, Chuang verfasserin aut Flagella hook protein FlgE is a novel vaccine candidate of 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. Genomic library Antigen screening FlgE Pneumonia Gao, Chen verfasserin aut Xie, Qin verfasserin aut Wang, Yin verfasserin aut Cheng, Xin verfasserin aut Fang, Yao verfasserin aut Liu, Zhiyong verfasserin aut Zhang, Weijun verfasserin aut Zou, Quanming verfasserin aut Lu, Guangwen verfasserin (orcid)0000-0001-7568-592X aut Gu, Jiang verfasserin aut Enthalten in Vaccine Amsterdam : Elsevier, 1983 39, Seite 2386-2395 Online-Ressource (DE-627)266886078 (DE-600)1468474-3 (DE-576)075961857 1873-2518 nnns volume:39 pages:2386-2395 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.45 Immunologie AR 39 2386-2395 |
allfieldsGer |
10.1016/j.vaccine.2021.03.051 doi (DE-627)ELV005819954 (ELSEVIER)S0264-410X(21)00344-3 DE-627 ger DE-627 rda eng 610 DE-600 44.45 bkl Wan, Chuang verfasserin aut Flagella hook protein FlgE is a novel vaccine candidate of 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. Genomic library Antigen screening FlgE Pneumonia Gao, Chen verfasserin aut Xie, Qin verfasserin aut Wang, Yin verfasserin aut Cheng, Xin verfasserin aut Fang, Yao verfasserin aut Liu, Zhiyong verfasserin aut Zhang, Weijun verfasserin aut Zou, Quanming verfasserin aut Lu, Guangwen verfasserin (orcid)0000-0001-7568-592X aut Gu, Jiang verfasserin aut Enthalten in Vaccine Amsterdam : Elsevier, 1983 39, Seite 2386-2395 Online-Ressource (DE-627)266886078 (DE-600)1468474-3 (DE-576)075961857 1873-2518 nnns volume:39 pages:2386-2395 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.45 Immunologie AR 39 2386-2395 |
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10.1016/j.vaccine.2021.03.051 doi (DE-627)ELV005819954 (ELSEVIER)S0264-410X(21)00344-3 DE-627 ger DE-627 rda eng 610 DE-600 44.45 bkl Wan, Chuang verfasserin aut Flagella hook protein FlgE is a novel vaccine candidate of 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. Genomic library Antigen screening FlgE Pneumonia Gao, Chen verfasserin aut Xie, Qin verfasserin aut Wang, Yin verfasserin aut Cheng, Xin verfasserin aut Fang, Yao verfasserin aut Liu, Zhiyong verfasserin aut Zhang, Weijun verfasserin aut Zou, Quanming verfasserin aut Lu, Guangwen verfasserin (orcid)0000-0001-7568-592X aut Gu, Jiang verfasserin aut Enthalten in Vaccine Amsterdam : Elsevier, 1983 39, Seite 2386-2395 Online-Ressource (DE-627)266886078 (DE-600)1468474-3 (DE-576)075961857 1873-2518 nnns volume:39 pages:2386-2395 GBV_USEFLAG_U SYSFLAG_U GBV_ELV GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_252 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.45 Immunologie AR 39 2386-2395 |
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Flagella hook protein FlgE is a novel vaccine candidate of |
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Wan, Chuang Gao, Chen Xie, Qin Wang, Yin Cheng, Xin Fang, Yao Liu, Zhiyong Zhang, Weijun Zou, Quanming Lu, Guangwen Gu, Jiang |
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Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. |
abstractGer |
Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. |
abstract_unstemmed |
Infections due to Pseudomonas aeruginosa (PA) are becoming a serious threat to patients in intensive care units. A PA vaccine is a practical and economical solution to solve the problems caused by PA infection successfully. In recent years, several antigen candidates have been tested in animal and human clinical trials, but none of them has been approved to date. An alternative strategy for antigen screening and protective antigens is in urgent demand. In this study, we generated a genome-wide library of PA protein fragments tagged with maltose-binding protein (MBP). Using sera from patients who recovered after PA infection, we identified a novel protective antigen, FlgE, which is the structural component of the flagella hook. Vaccination with recombinant FlgE (reFlgE) induced a Th2-predominant immune response and reduced bacterial load and inflammation in PA-infected mice. Anti-reFlgE antibodies recognized native FlgE on the bacterial membrane in vitro and conferred protection in mice, which may be due to the mediation of opsonophagocytic killing and inhibition of bacterial motility. In addition, the combination of reFlgE with rePcrVNH, an engineered antigen we reported previously, provided elevated protection against PA infection. Our data demonstrate that FlgE is a promising vaccine candidate for PA and provide a new strategy for the efficient screening of antigens of other pathogens. |
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