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- Title
Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.
- Authors
del Moral-Sánchez, Iván; Wee, Edmund G.; Xian, Yuejiao; Lee, Wen-Hsin; Allen, Joel D.; Torrents de la Peña, Alba; Fróes Rocha, Rebeca; Ferguson, James; León, André N.; Koekkoek, Sylvie; Schermer, Edith E.; Burger, Judith A.; Kumar, Sanjeev; Zwolsman, Robby; Brinkkemper, Mitch; Aartse, Aafke; Eggink, Dirk; Han, Julianna; Yuan, Meng; Crispin, Max
- 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.
- Subjects
INFLUENZA; HIV; VACCINES; TRIMERIZATION; HEMAGGLUTININ; VIRUS diseases
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-024-00862-8