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PreprintCited by 14HIV Research and TreatmentSARS-CoV-2 and COVID-19 ResearchInfluenza Virus Research Studies

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

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del Moral-Sánchez, Iván, Wee, Edmund G., Xian, Yuejiao, Lee, Wen-Hsin, Allen, Joel D., Torrents de la Peña, Alba, Rocha, Rebeca Fróes, 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, Ozorowski, Gabriel, Ward, Andrew B., Wilson, Ian A., Hanke, Tomáš, Sliepen, Kwinten, Sanders, Rogier W.·2023·npj Vaccines
DOI 10.1101/2023.08.27.554987PMC PMC10998906

Preprint — published as 10.1038/s41541-024-00862-8 · Paper page

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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.

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Metadata

Authors
del Moral-Sánchez, I., Wee, E. G., Xian, Y., Lee, W.-H., Allen, J. D., Torrents de la Peña, A., Rocha, R. F., Ferguson, J., León, A. N., Koekkoek, S., Schermer, E. E., Burger, J. A., Kumar, S., Zwolsman, R., Brinkkemper, M., Aartse, A., Eggink, D., Han, J., Yuan, M., Crispin, M., Ozorowski, G., Ward, A. B., Wilson, I. A., Hanke, T., Sliepen, K., & Sanders, R. W.
Affiliations
  • Amsterdam University Medical Centers (NL)
  • University of Oxford (GB)
  • Scripps Research Institute (US)
  • University of Southampton (GB)
  • Biomedical Primate Research Centre (NL)
  • Cornell University (US)
Corresponding author
Sanders, Rogier W.
ORCID
Venue
npj Vaccines
Publisher
openRxiv
Published
2023-08-27
Volume
9
Issue
1
Pages
74-74
ISSN
2059-0105 (ISSN-L)
DOI
10.1101/2023.08.27.554987
PMC
PMC10998906
OpenAlex
W4394014785
Cited by
14
References
1
Citations by year
2026: 3 · 2025: 9 · 2024: 2
FWCI
3.24
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • npj Vaccines (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion, cc-by)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Energy (76SF00515, DE–AC02–76SF00515, P41GM103393, AC02‐76SF00515, DE-AC02-)
  • Bill and Melinda Gates Foundation (OPP1111923 and OPP1132237, OPP1111923, OPP1115782, OPP1132237)
  • International AIDS Vaccine Initiative (OPP1115782, PGT145)
  • European Molecular Biology Organization (STS-7814)
  • Aids Fonds (2016019)
  • European Commission (HORIZON2020, 681137, DE-AC02-76SF00515)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • National Institutes of Health (DE-AC02-76SF00515, AI110657)
  • Office of Science (AC02-76SF00515, P41GM103393, DE-AC02-76SF0051 5, DE-AC02, 76SF00515)
  • University of California, San Francisco (NIH P41-GM103311, P41-GM103311)
  • National Institute of General Medical Sciences (GM103311, P41GM103311, NIH P41-GM103311, DE-AC02-76SF00515, P41GM103393)
  • National Institute of Allergy and Infectious Diseases (P01AI110657)
  • Basic Energy Sciences (DE-AC02, P41GM103393, 76SF00515, AC02-76SF00515, DE-AC-02-76SF00515)
  • Biological and Environmental Research (P41 GM103393, DE- AC0276SF00515)
  • SLAC National Accelerator Laboratory (DEAC02−76SF00515, AC02‐76SF00515, P41GM103393)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
Keywords
HIV-1 envelope glycoprotein, influenza hemagglutinin, nucleic acid-based vaccines, broadly neutralizing antibodies, SOSIP trimers, viral vector vaccines, trimerization domain, immunogen design

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