The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization
Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mec...
Ausführliche Beschreibung
Autor*in: |
Lin Lei [verfasserIn] Yuhe R. Yang [verfasserIn] Karen Tran [verfasserIn] Yimeng Wang [verfasserIn] Chi-I Chiang [verfasserIn] Gabriel Ozorowski [verfasserIn] Yongli Xiao [verfasserIn] Andrew B. Ward [verfasserIn] Richard T. Wyatt [verfasserIn] Yuxing Li [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Übergeordnetes Werk: |
In: Cell Reports - Elsevier, 2015, 27(2019), 2, Seite 586-598.e6 |
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Übergeordnetes Werk: |
volume:27 ; year:2019 ; number:2 ; pages:586-598.e6 |
Links: |
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DOI / URN: |
10.1016/j.celrep.2019.03.039 |
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Katalog-ID: |
DOAJ05229417X |
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520 | |a Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. | ||
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10.1016/j.celrep.2019.03.039 doi (DE-627)DOAJ05229417X (DE-599)DOAJcd35540b9b3146f085f6db86ae7701bc DE-627 ger DE-627 rakwb eng QH301-705.5 Lin Lei verfasserin aut The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. Biology (General) Yuhe R. Yang verfasserin aut Karen Tran verfasserin aut Yimeng Wang verfasserin aut Chi-I Chiang verfasserin aut Gabriel Ozorowski verfasserin aut Yongli Xiao verfasserin aut Andrew B. Ward verfasserin aut Richard T. Wyatt verfasserin aut Yuxing Li verfasserin aut In Cell Reports Elsevier, 2015 27(2019), 2, Seite 586-598.e6 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:27 year:2019 number:2 pages:586-598.e6 https://doi.org/10.1016/j.celrep.2019.03.039 kostenfrei https://doaj.org/article/cd35540b9b3146f085f6db86ae7701bc kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124719303559 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 27 2019 2 586-598.e6 |
spelling |
10.1016/j.celrep.2019.03.039 doi (DE-627)DOAJ05229417X (DE-599)DOAJcd35540b9b3146f085f6db86ae7701bc DE-627 ger DE-627 rakwb eng QH301-705.5 Lin Lei verfasserin aut The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. Biology (General) Yuhe R. Yang verfasserin aut Karen Tran verfasserin aut Yimeng Wang verfasserin aut Chi-I Chiang verfasserin aut Gabriel Ozorowski verfasserin aut Yongli Xiao verfasserin aut Andrew B. Ward verfasserin aut Richard T. Wyatt verfasserin aut Yuxing Li verfasserin aut In Cell Reports Elsevier, 2015 27(2019), 2, Seite 586-598.e6 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:27 year:2019 number:2 pages:586-598.e6 https://doi.org/10.1016/j.celrep.2019.03.039 kostenfrei https://doaj.org/article/cd35540b9b3146f085f6db86ae7701bc kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124719303559 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 27 2019 2 586-598.e6 |
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10.1016/j.celrep.2019.03.039 doi (DE-627)DOAJ05229417X (DE-599)DOAJcd35540b9b3146f085f6db86ae7701bc DE-627 ger DE-627 rakwb eng QH301-705.5 Lin Lei verfasserin aut The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. Biology (General) Yuhe R. Yang verfasserin aut Karen Tran verfasserin aut Yimeng Wang verfasserin aut Chi-I Chiang verfasserin aut Gabriel Ozorowski verfasserin aut Yongli Xiao verfasserin aut Andrew B. Ward verfasserin aut Richard T. Wyatt verfasserin aut Yuxing Li verfasserin aut In Cell Reports Elsevier, 2015 27(2019), 2, Seite 586-598.e6 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:27 year:2019 number:2 pages:586-598.e6 https://doi.org/10.1016/j.celrep.2019.03.039 kostenfrei https://doaj.org/article/cd35540b9b3146f085f6db86ae7701bc kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124719303559 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 27 2019 2 586-598.e6 |
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10.1016/j.celrep.2019.03.039 doi (DE-627)DOAJ05229417X (DE-599)DOAJcd35540b9b3146f085f6db86ae7701bc DE-627 ger DE-627 rakwb eng QH301-705.5 Lin Lei verfasserin aut The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. Biology (General) Yuhe R. Yang verfasserin aut Karen Tran verfasserin aut Yimeng Wang verfasserin aut Chi-I Chiang verfasserin aut Gabriel Ozorowski verfasserin aut Yongli Xiao verfasserin aut Andrew B. Ward verfasserin aut Richard T. Wyatt verfasserin aut Yuxing Li verfasserin aut In Cell Reports Elsevier, 2015 27(2019), 2, Seite 586-598.e6 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:27 year:2019 number:2 pages:586-598.e6 https://doi.org/10.1016/j.celrep.2019.03.039 kostenfrei https://doaj.org/article/cd35540b9b3146f085f6db86ae7701bc kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124719303559 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 27 2019 2 586-598.e6 |
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10.1016/j.celrep.2019.03.039 doi (DE-627)DOAJ05229417X (DE-599)DOAJcd35540b9b3146f085f6db86ae7701bc DE-627 ger DE-627 rakwb eng QH301-705.5 Lin Lei verfasserin aut The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. Biology (General) Yuhe R. Yang verfasserin aut Karen Tran verfasserin aut Yimeng Wang verfasserin aut Chi-I Chiang verfasserin aut Gabriel Ozorowski verfasserin aut Yongli Xiao verfasserin aut Andrew B. Ward verfasserin aut Richard T. Wyatt verfasserin aut Yuxing Li verfasserin aut In Cell Reports Elsevier, 2015 27(2019), 2, Seite 586-598.e6 (DE-627)684964562 (DE-600)2649101-1 22111247 nnns volume:27 year:2019 number:2 pages:586-598.e6 https://doi.org/10.1016/j.celrep.2019.03.039 kostenfrei https://doaj.org/article/cd35540b9b3146f085f6db86ae7701bc kostenfrei http://www.sciencedirect.com/science/article/pii/S2211124719303559 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 27 2019 2 586-598.e6 |
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QH301-705.5 The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization |
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The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization |
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Lin Lei Yuhe R. Yang Karen Tran Yimeng Wang Chi-I Chiang Gabriel Ozorowski Yongli Xiao Andrew B. Ward Richard T. Wyatt Yuxing Li |
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hiv-1 envelope glycoprotein c3/v4 region defines a prevalent neutralization epitope following immunization |
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The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization |
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Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. |
abstractGer |
Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. |
abstract_unstemmed |
Summary: Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design. : Lei et al. find that monoclonal antibodies elicited by an HIV-1 Env immunogen in guinea pigs converge on the Env C3/V4 region, similar to antibody responses that occur in HIV natural infections. Molecular and computational analyses suggest that the HIV Env C3/V4 region may be exploited as a vaccine target. |
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The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization |
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score |
7.4011116 |