National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
P01 AI110657
United States
Citation
Journal: NPJ Vaccines / Year: 2024 Title: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines. Authors: 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 / ...Authors: 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 / 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 ...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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