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NPJ Vaccines
. 2024 Apr 6;9(1):74.
doi: 10.1038/s41541-024-00862-8. Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines
Iván Del Moral-Sánchez 1 2 , Edmund G Wee # 3 , Yuejiao Xian # 4 , Wen-Hsin Lee 4 , Joel D Allen 5 , Alba Torrents de la Peña 4 , Rebeca Fróes Rocha 4 , James Ferguson 4 , André N León 4 , Sylvie Koekkoek 1 2 , Edith E Schermer 1 2 , Judith A Burger 1 2 , Sanjeev Kumar 1 2 6 , Robby Zwolsman 1 2 , Mitch Brinkkemper 1 2 , Aafke Aartse 1 7 , Dirk Eggink 1 2 , Julianna Han 4 , Meng Yuan 4 , Max Crispin 5 , Gabriel Ozorowski 4 , Andrew B Ward 4 , Ian A Wilson 4 , Tomáš Hanke 3 8 , Kwinten Sliepen 1 2 , Rogier W Sanders 9 10 11
Affiliations
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.
© 2024. The Author(s).
. 2024 Apr 6;9(1):74.
doi: 10.1038/s41541-024-00862-8. Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines
Iván Del Moral-Sánchez 1 2 , Edmund G Wee # 3 , Yuejiao Xian # 4 , Wen-Hsin Lee 4 , Joel D Allen 5 , Alba Torrents de la Peña 4 , Rebeca Fróes Rocha 4 , James Ferguson 4 , André N León 4 , Sylvie Koekkoek 1 2 , Edith E Schermer 1 2 , Judith A Burger 1 2 , Sanjeev Kumar 1 2 6 , Robby Zwolsman 1 2 , Mitch Brinkkemper 1 2 , Aafke Aartse 1 7 , Dirk Eggink 1 2 , Julianna Han 4 , Meng Yuan 4 , Max Crispin 5 , Gabriel Ozorowski 4 , Andrew B Ward 4 , Ian A Wilson 4 , Tomáš Hanke 3 8 , Kwinten Sliepen 1 2 , Rogier W Sanders 9 10 11
Affiliations
- PMID: 38582771
- PMCID: PMC10998906
- DOI: 10.1038/s41541-024-00862-8
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.
© 2024. The Author(s).