Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines

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 CrispinGabriel Ozorowski, Andrew B. Ward, Ian A. Wilson, Tomáš Hanke, Kwinten Sliepen, Rogier W. Sanders

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Article number74
Journalnpj Vaccines
Issue number1
Publication statusPublished - 1 Dec 2024

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