Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines
Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trim...
Ausführliche Beschreibung
Autor*in: |
Iván del Moral-Sánchez [verfasserIn] Edmund G. Wee [verfasserIn] Yuejiao Xian [verfasserIn] Wen-Hsin Lee [verfasserIn] Joel D. Allen [verfasserIn] Alba Torrents de la Peña [verfasserIn] Rebeca Fróes Rocha [verfasserIn] James Ferguson [verfasserIn] André N. León [verfasserIn] Sylvie Koekkoek [verfasserIn] Edith E. Schermer [verfasserIn] Judith A. Burger [verfasserIn] Sanjeev Kumar [verfasserIn] Robby Zwolsman [verfasserIn] Mitch Brinkkemper [verfasserIn] Aafke Aartse [verfasserIn] Dirk Eggink [verfasserIn] Julianna Han [verfasserIn] Meng Yuan [verfasserIn] Max Crispin [verfasserIn] Gabriel Ozorowski [verfasserIn] Andrew B. Ward [verfasserIn] Ian A. Wilson [verfasserIn] Tomáš Hanke [verfasserIn] Kwinten Sliepen [verfasserIn] Rogier W. Sanders [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2024 |
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Übergeordnetes Werk: |
In: npj Vaccines - Nature Portfolio, 2017, 9(2024), 1, Seite 18 |
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Übergeordnetes Werk: |
volume:9 ; year:2024 ; number:1 ; pages:18 |
Links: |
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DOI / URN: |
10.1038/s41541-024-00862-8 |
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Katalog-ID: |
DOAJ095870989 |
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520 | |a Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. | ||
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10.1038/s41541-024-00862-8 doi (DE-627)DOAJ095870989 (DE-599)DOAJ9406da7e97304295838f177acd6e13b0 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Iván del Moral-Sánchez verfasserin aut Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edmund G. Wee verfasserin aut Yuejiao Xian verfasserin aut Wen-Hsin Lee verfasserin aut Joel D. Allen verfasserin aut Alba Torrents de la Peña verfasserin aut Rebeca Fróes Rocha verfasserin aut James Ferguson verfasserin aut André N. León verfasserin aut Sylvie Koekkoek verfasserin aut Edith E. Schermer verfasserin aut Judith A. Burger verfasserin aut Sanjeev Kumar verfasserin aut Robby Zwolsman verfasserin aut Mitch Brinkkemper verfasserin aut Aafke Aartse verfasserin aut Dirk Eggink verfasserin aut Julianna Han verfasserin aut Meng Yuan verfasserin aut Max Crispin verfasserin aut Gabriel Ozorowski verfasserin aut Andrew B. Ward verfasserin aut Ian A. Wilson verfasserin aut Tomáš Hanke verfasserin aut Kwinten Sliepen verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 18 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:18 https://doi.org/10.1038/s41541-024-00862-8 kostenfrei https://doaj.org/article/9406da7e97304295838f177acd6e13b0 kostenfrei https://doi.org/10.1038/s41541-024-00862-8 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 9 2024 1 18 |
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10.1038/s41541-024-00862-8 doi (DE-627)DOAJ095870989 (DE-599)DOAJ9406da7e97304295838f177acd6e13b0 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Iván del Moral-Sánchez verfasserin aut Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edmund G. Wee verfasserin aut Yuejiao Xian verfasserin aut Wen-Hsin Lee verfasserin aut Joel D. Allen verfasserin aut Alba Torrents de la Peña verfasserin aut Rebeca Fróes Rocha verfasserin aut James Ferguson verfasserin aut André N. León verfasserin aut Sylvie Koekkoek verfasserin aut Edith E. Schermer verfasserin aut Judith A. Burger verfasserin aut Sanjeev Kumar verfasserin aut Robby Zwolsman verfasserin aut Mitch Brinkkemper verfasserin aut Aafke Aartse verfasserin aut Dirk Eggink verfasserin aut Julianna Han verfasserin aut Meng Yuan verfasserin aut Max Crispin verfasserin aut Gabriel Ozorowski verfasserin aut Andrew B. Ward verfasserin aut Ian A. Wilson verfasserin aut Tomáš Hanke verfasserin aut Kwinten Sliepen verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 18 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:18 https://doi.org/10.1038/s41541-024-00862-8 kostenfrei https://doaj.org/article/9406da7e97304295838f177acd6e13b0 kostenfrei https://doi.org/10.1038/s41541-024-00862-8 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 9 2024 1 18 |
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10.1038/s41541-024-00862-8 doi (DE-627)DOAJ095870989 (DE-599)DOAJ9406da7e97304295838f177acd6e13b0 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Iván del Moral-Sánchez verfasserin aut Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edmund G. Wee verfasserin aut Yuejiao Xian verfasserin aut Wen-Hsin Lee verfasserin aut Joel D. Allen verfasserin aut Alba Torrents de la Peña verfasserin aut Rebeca Fróes Rocha verfasserin aut James Ferguson verfasserin aut André N. León verfasserin aut Sylvie Koekkoek verfasserin aut Edith E. Schermer verfasserin aut Judith A. Burger verfasserin aut Sanjeev Kumar verfasserin aut Robby Zwolsman verfasserin aut Mitch Brinkkemper verfasserin aut Aafke Aartse verfasserin aut Dirk Eggink verfasserin aut Julianna Han verfasserin aut Meng Yuan verfasserin aut Max Crispin verfasserin aut Gabriel Ozorowski verfasserin aut Andrew B. Ward verfasserin aut Ian A. Wilson verfasserin aut Tomáš Hanke verfasserin aut Kwinten Sliepen verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 18 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:18 https://doi.org/10.1038/s41541-024-00862-8 kostenfrei https://doaj.org/article/9406da7e97304295838f177acd6e13b0 kostenfrei https://doi.org/10.1038/s41541-024-00862-8 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 9 2024 1 18 |
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10.1038/s41541-024-00862-8 doi (DE-627)DOAJ095870989 (DE-599)DOAJ9406da7e97304295838f177acd6e13b0 DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Iván del Moral-Sánchez verfasserin aut Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Edmund G. Wee verfasserin aut Yuejiao Xian verfasserin aut Wen-Hsin Lee verfasserin aut Joel D. Allen verfasserin aut Alba Torrents de la Peña verfasserin aut Rebeca Fróes Rocha verfasserin aut James Ferguson verfasserin aut André N. León verfasserin aut Sylvie Koekkoek verfasserin aut Edith E. Schermer verfasserin aut Judith A. Burger verfasserin aut Sanjeev Kumar verfasserin aut Robby Zwolsman verfasserin aut Mitch Brinkkemper verfasserin aut Aafke Aartse verfasserin aut Dirk Eggink verfasserin aut Julianna Han verfasserin aut Meng Yuan verfasserin aut Max Crispin verfasserin aut Gabriel Ozorowski verfasserin aut Andrew B. Ward verfasserin aut Ian A. Wilson verfasserin aut Tomáš Hanke verfasserin aut Kwinten Sliepen verfasserin aut Rogier W. Sanders verfasserin aut In npj Vaccines Nature Portfolio, 2017 9(2024), 1, Seite 18 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:9 year:2024 number:1 pages:18 https://doi.org/10.1038/s41541-024-00862-8 kostenfrei https://doaj.org/article/9406da7e97304295838f177acd6e13b0 kostenfrei https://doi.org/10.1038/s41541-024-00862-8 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 9 2024 1 18 |
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Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
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Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
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Iván del Moral-Sánchez |
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Iván del Moral-Sánchez Edmund G. Wee Yuejiao Xian Wen-Hsin Lee Joel D. Allen Alba Torrents de la Peña Rebeca Fróes Rocha James Ferguson André N. León Sylvie Koekkoek Edith E. Schermer Judith A. Burger Sanjeev Kumar Robby Zwolsman Mitch Brinkkemper Aafke Aartse Dirk Eggink Julianna Han Meng Yuan Max Crispin Gabriel Ozorowski Andrew B. Ward Ian A. Wilson Tomáš Hanke Kwinten Sliepen Rogier W. Sanders |
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Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
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Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. |
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Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. |
abstract_unstemmed |
Abstract Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies. |
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Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
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Edmund G. Wee Yuejiao Xian Wen-Hsin Lee Joel D. Allen Alba Torrents de la Peña Rebeca Fróes Rocha James Ferguson André N. León Sylvie Koekkoek Edith E. Schermer Judith A. Burger Sanjeev Kumar Robby Zwolsman Mitch Brinkkemper Aafke Aartse Dirk Eggink Julianna Han Meng Yuan Max Crispin Gabriel Ozorowski Andrew B. Ward Ian A. Wilson Tomáš Hanke Kwinten Sliepen Rogier W. Sanders |
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