tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Edmund G Wee[SUP] #[/SUP][SUP] 3 [/SUP], Yuejiao Xian[SUP] #[/SUP][SUP] 4 [/SUP], Wen-Hsin Lee[SUP] 4 [/SUP], Joel D Allen[SUP] 5 [/SUP], Alba Torrents de la Peña[SUP] 4 [/SUP], Rebeca Fróes Rocha[SUP] 4 [/SUP], James Ferguson[SUP] 4 [/SUP], André N León[SUP] 4 [/SUP], Sylvie Koekkoek[SUP] 1 2 [/SUP], Edith E Schermer[SUP] 1 2 [/SUP], Judith A Burger[SUP] 1 2 [/SUP], Sanjeev Kumar[SUP] 1 2 6 [/SUP], Robby Zwolsman[SUP] 1 2 [/SUP], Mitch Brinkkemper[SUP] 1 2 [/SUP], Aafke Aartse[SUP] 1 7 [/SUP], Dirk Eggink[SUP] 1 2 [/SUP], Julianna Han[SUP] 4 [/SUP], Meng Yuan[SUP] 4 [/SUP], Max Crispin[SUP] 5 [/SUP], Gabriel Ozorowski[SUP] 4 [/SUP], Andrew B Ward[SUP] 4 [/SUP], Ian A Wilson[SUP] 4 [/SUP], Tomáš Hanke[SUP] 3 8 [/SUP], Kwinten Sliepen[SUP] 1 2 [/SUP], Rogier W Sanders[SUP] 9 10 11 [/SUP]
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[SUP] 1 2 [/SUP], Edmund G Wee[SUP] #[/SUP][SUP] 3 [/SUP], Yuejiao Xian[SUP] #[/SUP][SUP] 4 [/SUP], Wen-Hsin Lee[SUP] 4 [/SUP], Joel D Allen[SUP] 5 [/SUP], Alba Torrents de la Peña[SUP] 4 [/SUP], Rebeca Fróes Rocha[SUP] 4 [/SUP], James Ferguson[SUP] 4 [/SUP], André N León[SUP] 4 [/SUP], Sylvie Koekkoek[SUP] 1 2 [/SUP], Edith E Schermer[SUP] 1 2 [/SUP], Judith A Burger[SUP] 1 2 [/SUP], Sanjeev Kumar[SUP] 1 2 6 [/SUP], Robby Zwolsman[SUP] 1 2 [/SUP], Mitch Brinkkemper[SUP] 1 2 [/SUP], Aafke Aartse[SUP] 1 7 [/SUP], Dirk Eggink[SUP] 1 2 [/SUP], Julianna Han[SUP] 4 [/SUP], Meng Yuan[SUP] 4 [/SUP], Max Crispin[SUP] 5 [/SUP], Gabriel Ozorowski[SUP] 4 [/SUP], Andrew B Ward[SUP] 4 [/SUP], Ian A Wilson[SUP] 4 [/SUP], Tomáš Hanke[SUP] 3 8 [/SUP], Kwinten Sliepen[SUP] 1 2 [/SUP], Rogier W Sanders[SUP] 9 10 11 [/SUP]
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).