Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivale...
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Autor*in:	Philip J. M. Brouwer [verfasserIn] Aleksandar Antanasijevic [verfasserIn] Marlon de Gast [verfasserIn] Joel D. Allen [verfasserIn] Tom P. L. Bijl [verfasserIn] Anila Yasmeen [verfasserIn] Rashmi Ravichandran [verfasserIn] Judith A. Burger [verfasserIn] Gabriel Ozorowski [verfasserIn] Jonathan L. Torres [verfasserIn] Celia LaBranche [verfasserIn] David C. Montefiori [verfasserIn] Rajesh P. Ringe [verfasserIn] Marit J. van Gils [verfasserIn] John P. Moore [verfasserIn] Per Johan Klasse [verfasserIn] Max Crispin [verfasserIn] Neil P. King [verfasserIn] Andrew B. Ward [verfasserIn] Rogier W. Sanders [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: npj Vaccines - Nature Portfolio, 2017, 6(2021), 1, Seite 14
Übergeordnetes Werk:	volume:6 ; year:2021 ; number:1 ; pages:14

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41541-021-00285-9

Katalog-ID:	DOAJ061229946

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520			\|a Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.
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allfields	10.1038/s41541-021-00285-9 doi (DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Philip J. M. Brouwer verfasserin aut Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Aleksandar Antanasijevic verfasserin aut Marlon de Gast verfasserin aut Joel D. Allen verfasserin aut Tom P. L. Bijl verfasserin aut Anila Yasmeen verfasserin aut Rashmi Ravichandran verfasserin aut Judith A. Burger verfasserin aut Gabriel Ozorowski verfasserin aut Jonathan L. Torres verfasserin aut Celia LaBranche verfasserin aut David C. Montefiori verfasserin aut Rajesh P. Ringe verfasserin aut Marit J. van Gils verfasserin aut John P. Moore verfasserin aut Per Johan Klasse verfasserin aut Max Crispin verfasserin aut Neil P. King verfasserin aut Andrew B. Ward verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 14 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:14 https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d kostenfrei https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 14
spelling	10.1038/s41541-021-00285-9 doi (DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Philip J. M. Brouwer verfasserin aut Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Aleksandar Antanasijevic verfasserin aut Marlon de Gast verfasserin aut Joel D. Allen verfasserin aut Tom P. L. Bijl verfasserin aut Anila Yasmeen verfasserin aut Rashmi Ravichandran verfasserin aut Judith A. Burger verfasserin aut Gabriel Ozorowski verfasserin aut Jonathan L. Torres verfasserin aut Celia LaBranche verfasserin aut David C. Montefiori verfasserin aut Rajesh P. Ringe verfasserin aut Marit J. van Gils verfasserin aut John P. Moore verfasserin aut Per Johan Klasse verfasserin aut Max Crispin verfasserin aut Neil P. King verfasserin aut Andrew B. Ward verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 14 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:14 https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d kostenfrei https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 14
allfields_unstemmed	10.1038/s41541-021-00285-9 doi (DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Philip J. M. Brouwer verfasserin aut Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Aleksandar Antanasijevic verfasserin aut Marlon de Gast verfasserin aut Joel D. Allen verfasserin aut Tom P. L. Bijl verfasserin aut Anila Yasmeen verfasserin aut Rashmi Ravichandran verfasserin aut Judith A. Burger verfasserin aut Gabriel Ozorowski verfasserin aut Jonathan L. Torres verfasserin aut Celia LaBranche verfasserin aut David C. Montefiori verfasserin aut Rajesh P. Ringe verfasserin aut Marit J. van Gils verfasserin aut John P. Moore verfasserin aut Per Johan Klasse verfasserin aut Max Crispin verfasserin aut Neil P. King verfasserin aut Andrew B. Ward verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 14 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:14 https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d kostenfrei https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 14
allfieldsGer	10.1038/s41541-021-00285-9 doi (DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Philip J. M. Brouwer verfasserin aut Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Aleksandar Antanasijevic verfasserin aut Marlon de Gast verfasserin aut Joel D. Allen verfasserin aut Tom P. L. Bijl verfasserin aut Anila Yasmeen verfasserin aut Rashmi Ravichandran verfasserin aut Judith A. Burger verfasserin aut Gabriel Ozorowski verfasserin aut Jonathan L. Torres verfasserin aut Celia LaBranche verfasserin aut David C. Montefiori verfasserin aut Rajesh P. Ringe verfasserin aut Marit J. van Gils verfasserin aut John P. Moore verfasserin aut Per Johan Klasse verfasserin aut Max Crispin verfasserin aut Neil P. King verfasserin aut Andrew B. Ward verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 14 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:14 https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d kostenfrei https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 14
allfieldsSound	10.1038/s41541-021-00285-9 doi (DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Philip J. M. Brouwer verfasserin aut Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Aleksandar Antanasijevic verfasserin aut Marlon de Gast verfasserin aut Joel D. Allen verfasserin aut Tom P. L. Bijl verfasserin aut Anila Yasmeen verfasserin aut Rashmi Ravichandran verfasserin aut Judith A. Burger verfasserin aut Gabriel Ozorowski verfasserin aut Jonathan L. Torres verfasserin aut Celia LaBranche verfasserin aut David C. Montefiori verfasserin aut Rajesh P. Ringe verfasserin aut Marit J. van Gils verfasserin aut John P. Moore verfasserin aut Per Johan Klasse verfasserin aut Max Crispin verfasserin aut Neil P. King verfasserin aut Andrew B. Ward verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 14 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:14 https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d kostenfrei https://doi.org/10.1038/s41541-021-00285-9 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 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_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 14
language	English
source	In npj Vaccines 6(2021), 1, Seite 14 volume:6 year:2021 number:1 pages:14
sourceStr	In npj Vaccines 6(2021), 1, Seite 14 volume:6 year:2021 number:1 pages:14
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	npj Vaccines
authorswithroles_txt_mv	Philip J. M. Brouwer @@aut@@ Aleksandar Antanasijevic @@aut@@ Marlon de Gast @@aut@@ Joel D. Allen @@aut@@ Tom P. L. Bijl @@aut@@ Anila Yasmeen @@aut@@ Rashmi Ravichandran @@aut@@ Judith A. Burger @@aut@@ Gabriel Ozorowski @@aut@@ Jonathan L. Torres @@aut@@ Celia LaBranche @@aut@@ David C. Montefiori @@aut@@ Rajesh P. Ringe @@aut@@ Marit J. van Gils @@aut@@ John P. Moore @@aut@@ Per Johan Klasse @@aut@@ Max Crispin @@aut@@ Neil P. King @@aut@@ Andrew B. Ward @@aut@@ Rogier W. Sanders @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	87811839X
id	DOAJ061229946
language_de	englisch
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callnumber-first	R - Medicine
author	Philip J. M. Brouwer
spellingShingle	Philip J. M. Brouwer misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
authorStr	Philip J. M. Brouwer
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topic_title	RC581-607 RC254-282 Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
topic	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
ctrlnum	(DE-627)DOAJ061229946 (DE-599)DOAJ6d2ce266cff0455eb80fcc32049d700d
title_full	Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
author_sort	Philip J. M. Brouwer
journal	npj Vaccines
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author_browse	Philip J. M. Brouwer Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders
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author-letter	Philip J. M. Brouwer
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title_sort	immunofocusing and enhancing autologous tier-2 hiv-1 neutralization by displaying env trimers on two-component protein nanoparticles
callnumber	RC581-607
title_auth	Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
abstract	Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.
abstractGer	Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.
abstract_unstemmed	Abstract The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.
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title_short	Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles
url	https://doi.org/10.1038/s41541-021-00285-9 https://doaj.org/article/6d2ce266cff0455eb80fcc32049d700d https://doaj.org/toc/2059-0105
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author2	Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders
author2Str	Aleksandar Antanasijevic Marlon de Gast Joel D. Allen Tom P. L. Bijl Anila Yasmeen Rashmi Ravichandran Judith A. Burger Gabriel Ozorowski Jonathan L. Torres Celia LaBranche David C. Montefiori Rajesh P. Ringe Marit J. van Gils John P. Moore Per Johan Klasse Max Crispin Neil P. King Andrew B. Ward Rogier W. Sanders
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doi_str	10.1038/s41541-021-00285-9
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up_date	2024-07-03T19:33:50.430Z
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