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TitleTriple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines.
Journal, issue, pagesNPJ Vaccines, Vol. 9, Issue 1, Page 74, Year 2024
Publish dateApr 6, 2024
AuthorsIván 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 /
PubMed AbstractRecombinant 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.
External linksNPJ Vaccines / PubMed:38582771 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution5.75 - 28.52 Å
Structure data

EMDB-42464: chEnv TTT protein in complex with 43A2 Fab
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-42468: chEnv TTT protein in complex with CM01A Fab
Method: EM (single particle) / Resolution: 28.0 Å

EMDB-43664: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines
Method: EM (single particle) / Resolution: 28.52 Å

EMDB-43665: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines (cH125 TTT)
Method: EM (single particle) / Resolution: 17.82 Å

EMDB-43666: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines (H2/1 GCN4)
Method: EM (single particle) / Resolution: 19.52 Å

EMDB-43668: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines (H5/1 GCN4)
Method: EM (single particle) / Resolution: 19.52 Å

EMDB-43669: Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines. H5 GCN4
Method: EM (single particle) / Resolution: 24.72 Å

PDB-8tgo:
Crystal structure of the BG505 triple tandem trimer gp140 HIV-1 Env in complex with PGT124 and 35O22
Method: X-RAY DIFFRACTION / Resolution: 5.75 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • human immunodeficiency virus 1
  • Macaca mulatta (Rhesus monkey)
  • Influenza A virus
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV / envelope / antibody / VIRAL PROTEIN-IMMUNE SYSTEM complex

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