Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers
Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Yoann Aldon [verfasserIn] Paul F. McKay [verfasserIn] Joel Allen [verfasserIn] Gabriel Ozorowski [verfasserIn] Réka Felfödiné Lévai [verfasserIn] Monica Tolazzi [verfasserIn] Paul Rogers [verfasserIn] Linling He [verfasserIn] Natalia de Val [verfasserIn] Katalin Fábián [verfasserIn] Gabriella Scarlatti [verfasserIn] Jiang Zhu [verfasserIn] Andrew B. Ward [verfasserIn] Max Crispin [verfasserIn] Robin J. Shattock [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018 |
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| Übergeordnetes Werk: |
In: Cell Reports - Elsevier, 2015, 24(2018), 12, Seite 3324-3338.e5 |
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| Übergeordnetes Werk: |
volume:24 ; year:2018 ; number:12 ; pages:3324-3338.e5 |
| Links: |
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| DOI / URN: |
10.1016/j.celrep.2018.08.051 |
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| Katalog-ID: |
DOAJ055510264 |
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| 520 | |a Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane | ||
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| 700 | 0 | |a Joel Allen |e verfasserin |4 aut | |
| 700 | 0 | |a Gabriel Ozorowski |e verfasserin |4 aut | |
| 700 | 0 | |a Réka Felfödiné Lévai |e verfasserin |4 aut | |
| 700 | 0 | |a Monica Tolazzi |e verfasserin |4 aut | |
| 700 | 0 | |a Paul Rogers |e verfasserin |4 aut | |
| 700 | 0 | |a Linling He |e verfasserin |4 aut | |
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| 700 | 0 | |a Katalin Fábián |e verfasserin |4 aut | |
| 700 | 0 | |a Gabriella Scarlatti |e verfasserin |4 aut | |
| 700 | 0 | |a Jiang Zhu |e verfasserin |4 aut | |
| 700 | 0 | |a Andrew B. Ward |e verfasserin |4 aut | |
| 700 | 0 | |a Max Crispin |e verfasserin |4 aut | |
| 700 | 0 | |a Robin J. Shattock |e verfasserin |4 aut | |
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10.1016/j.celrep.2018.08.051 doi (DE-627)DOAJ055510264 (DE-599)DOAJfb523e9dda444aac877d8ad10ccabd5b DE-627 ger DE-627 rakwb eng QH301-705.5 Yoann Aldon verfasserin aut Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane Biology (General) Paul F. McKay verfasserin aut Joel Allen verfasserin aut Gabriel Ozorowski verfasserin aut Réka Felfödiné Lévai verfasserin aut Monica Tolazzi verfasserin aut Paul Rogers verfasserin aut Linling He verfasserin aut Natalia de Val verfasserin aut Katalin Fábián verfasserin aut Gabriella Scarlatti verfasserin aut Jiang Zhu verfasserin aut Andrew B. Ward verfasserin aut Max Crispin verfasserin aut Robin J. Shattock verfasserin aut In Cell Reports Elsevier, 2015 24(2018), 12, Seite 3324-3338.e5 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:24 year:2018 number:12 pages:3324-3338.e5 https://doi.org/10.1016/j.celrep.2018.08.051 kostenfrei https://doaj.org/article/fb523e9dda444aac877d8ad10ccabd5b kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124718313378 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2018 12 3324-3338.e5 |
| spelling |
10.1016/j.celrep.2018.08.051 doi (DE-627)DOAJ055510264 (DE-599)DOAJfb523e9dda444aac877d8ad10ccabd5b DE-627 ger DE-627 rakwb eng QH301-705.5 Yoann Aldon verfasserin aut Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane Biology (General) Paul F. McKay verfasserin aut Joel Allen verfasserin aut Gabriel Ozorowski verfasserin aut Réka Felfödiné Lévai verfasserin aut Monica Tolazzi verfasserin aut Paul Rogers verfasserin aut Linling He verfasserin aut Natalia de Val verfasserin aut Katalin Fábián verfasserin aut Gabriella Scarlatti verfasserin aut Jiang Zhu verfasserin aut Andrew B. Ward verfasserin aut Max Crispin verfasserin aut Robin J. Shattock verfasserin aut In Cell Reports Elsevier, 2015 24(2018), 12, Seite 3324-3338.e5 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:24 year:2018 number:12 pages:3324-3338.e5 https://doi.org/10.1016/j.celrep.2018.08.051 kostenfrei https://doaj.org/article/fb523e9dda444aac877d8ad10ccabd5b kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124718313378 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2018 12 3324-3338.e5 |
| allfields_unstemmed |
10.1016/j.celrep.2018.08.051 doi (DE-627)DOAJ055510264 (DE-599)DOAJfb523e9dda444aac877d8ad10ccabd5b DE-627 ger DE-627 rakwb eng QH301-705.5 Yoann Aldon verfasserin aut Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane Biology (General) Paul F. McKay verfasserin aut Joel Allen verfasserin aut Gabriel Ozorowski verfasserin aut Réka Felfödiné Lévai verfasserin aut Monica Tolazzi verfasserin aut Paul Rogers verfasserin aut Linling He verfasserin aut Natalia de Val verfasserin aut Katalin Fábián verfasserin aut Gabriella Scarlatti verfasserin aut Jiang Zhu verfasserin aut Andrew B. Ward verfasserin aut Max Crispin verfasserin aut Robin J. Shattock verfasserin aut In Cell Reports Elsevier, 2015 24(2018), 12, Seite 3324-3338.e5 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:24 year:2018 number:12 pages:3324-3338.e5 https://doi.org/10.1016/j.celrep.2018.08.051 kostenfrei https://doaj.org/article/fb523e9dda444aac877d8ad10ccabd5b kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124718313378 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2018 12 3324-3338.e5 |
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10.1016/j.celrep.2018.08.051 doi (DE-627)DOAJ055510264 (DE-599)DOAJfb523e9dda444aac877d8ad10ccabd5b DE-627 ger DE-627 rakwb eng QH301-705.5 Yoann Aldon verfasserin aut Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane Biology (General) Paul F. McKay verfasserin aut Joel Allen verfasserin aut Gabriel Ozorowski verfasserin aut Réka Felfödiné Lévai verfasserin aut Monica Tolazzi verfasserin aut Paul Rogers verfasserin aut Linling He verfasserin aut Natalia de Val verfasserin aut Katalin Fábián verfasserin aut Gabriella Scarlatti verfasserin aut Jiang Zhu verfasserin aut Andrew B. Ward verfasserin aut Max Crispin verfasserin aut Robin J. Shattock verfasserin aut In Cell Reports Elsevier, 2015 24(2018), 12, Seite 3324-3338.e5 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:24 year:2018 number:12 pages:3324-3338.e5 https://doi.org/10.1016/j.celrep.2018.08.051 kostenfrei https://doaj.org/article/fb523e9dda444aac877d8ad10ccabd5b kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124718313378 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2018 12 3324-3338.e5 |
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10.1016/j.celrep.2018.08.051 doi (DE-627)DOAJ055510264 (DE-599)DOAJfb523e9dda444aac877d8ad10ccabd5b DE-627 ger DE-627 rakwb eng QH301-705.5 Yoann Aldon verfasserin aut Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane Biology (General) Paul F. McKay verfasserin aut Joel Allen verfasserin aut Gabriel Ozorowski verfasserin aut Réka Felfödiné Lévai verfasserin aut Monica Tolazzi verfasserin aut Paul Rogers verfasserin aut Linling He verfasserin aut Natalia de Val verfasserin aut Katalin Fábián verfasserin aut Gabriella Scarlatti verfasserin aut Jiang Zhu verfasserin aut Andrew B. Ward verfasserin aut Max Crispin verfasserin aut Robin J. Shattock verfasserin aut In Cell Reports Elsevier, 2015 24(2018), 12, Seite 3324-3338.e5 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:24 year:2018 number:12 pages:3324-3338.e5 https://doi.org/10.1016/j.celrep.2018.08.051 kostenfrei https://doaj.org/article/fb523e9dda444aac877d8ad10ccabd5b kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124718313378 kostenfrei https://doaj.org/toc/2211-1247 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 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_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 24 2018 12 3324-3338.e5 |
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Yoann Aldon @@aut@@ Paul F. McKay @@aut@@ Joel Allen @@aut@@ Gabriel Ozorowski @@aut@@ Réka Felfödiné Lévai @@aut@@ Monica Tolazzi @@aut@@ Paul Rogers @@aut@@ Linling He @@aut@@ Natalia de Val @@aut@@ Katalin Fábián @@aut@@ Gabriella Scarlatti @@aut@@ Jiang Zhu @@aut@@ Andrew B. Ward @@aut@@ Max Crispin @@aut@@ Robin J. Shattock @@aut@@ |
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rational design of dna-expressed stabilized native-like hiv-1 envelope trimers |
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Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers |
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Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane |
| abstractGer |
Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane |
| abstract_unstemmed |
Summary: The HIV-1-envelope glycoprotein (Env) is the main target of antigen design for antibody-based prophylactic vaccines. The generation of broadly neutralizing antibodies (bNAb) likely requires the appropriate presentation of stabilized trimers preventing exposure of non-neutralizing antibody (nNAb) epitopes. We designed a series of membrane-bound Envs with increased trimer stability through the introduction of key stabilization mutations. We derived a stabilized HIV-1 trimer, ConSOSL.UFO.750, which displays a dramatic reduction in nNAb binding while maintaining high quaternary and MPER-specific bNAb binding. Its soluble counterpart, ConSOSL.UFO.664, displays similar antigenicity, and its native-like Env structure is confirmed by negative stain-EM and glycosylation profiling of the soluble ConSOSL.UFO.664 trimer. A rabbit immunization study demonstrated that the ConSOSL.UFO.664 can induce autologous tier 2 neutralization. We have successfully designed a stabilized native-like Env trimer amenable to nucleic acid or viral vector-based vaccination strategies. : Aldon et al. developed membrane-bound and soluble stabilized HIV-1 Env trimer immunogens suitable for DNA/RNA or viral vector vaccines. The sequential iterative design and analysis in muscle cells have the potential to be used as a generalizable method for the expression of stabilized native-like trimers. Keywords: HIV-1, Env, trimer, bNAb, DNA, cell-based ELISA, muscle cells, cytoplasmic tail, transmembrane |
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