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

Journal article

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.

Authors: del Moral-Sánchez, I; Wee, EG; Xian, Y; Lee, W-H; Allen, JD

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: npj Vaccines
• Volume: 9
• Issue: 1
• Pages: 74-74
• Article number: 74
• Publication date: 2024-04-06
• DOI: 10.1038/s41541-024-00862-8
• EISSN: 2059-0105
• ISSN: 2059-0105
• Language: English
• Keywords: Recombinant DNA; Gene; Hemagglutinin (influenza); Chemistry; Virus; Genetics; Antibody; Biology; Trimer; Dimer; Virology; Epitope; Glycoprotein; Computational biology; Gp41