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...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-024-00862-8 |
| _version_ | 1827291790736097280 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Iván del Moral-Sánchez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T12:43:48Z |
| format | Article |
| id | doaj.art-9406da7e97304295838f177acd6e13b0 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-04-24T12:43:48Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-9406da7e97304295838f177acd6e13b02024-04-07T11:07:37ZengNature Portfolionpj Vaccines2059-01052024-04-019111810.1038/s41541-024-00862-8Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccinesIván del Moral-Sánchez0Edmund G. Wee1Yuejiao Xian2Wen-Hsin Lee3Joel D. Allen4Alba Torrents de la Peña5Rebeca Fróes Rocha6James Ferguson7André N. León8Sylvie Koekkoek9Edith E. Schermer10Judith A. Burger11Sanjeev Kumar12Robby Zwolsman13Mitch Brinkkemper14Aafke Aartse15Dirk Eggink16Julianna Han17Meng Yuan18Max Crispin19Gabriel Ozorowski20Andrew B. Ward21Ian A. Wilson22Tomáš Hanke23Kwinten Sliepen24Rogier W. Sanders25Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamThe Jenner Institute, Nuffield Department of Medicine, University of OxfordDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteSchool of Biological Sciences, University of SouthamptonDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteSchool of Biological Sciences, University of SouthamptonDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteDepartment of Integrative Structural and Computational Biology, The Scripps Research InstituteThe Jenner Institute, Nuffield Department of Medicine, University of OxfordDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamDepartment of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of AmsterdamAbstract 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.https://doi.org/10.1038/s41541-024-00862-8 |
| spellingShingle | 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 Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines npj Vaccines |
| title | Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
| title_full | Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
| title_fullStr | Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
| title_full_unstemmed | Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
| title_short | Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines |
| title_sort | triple tandem trimer immunogens for hiv 1 and influenza nucleic acid based vaccines |
| url | https://doi.org/10.1038/s41541-024-00862-8 |
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