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Record W4394014785 · doi:10.1038/s41541-024-00862-8

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

2024· article· en· W4394014785 on OpenAlexaff
Iván del Moral-Sánchez, Edmund G. Wee, Yuejiao Xian, Wen-Hsin Lee, Joel D. Allen, Alba Torrents de la Peña, Rebeca de Paiva Fróes Rocha, James A. Ferguson, André Nicolás León, Sylvie M. 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

Bibliographic record

Venuenpj Vaccines · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsInstitute of Infection and Immunity
FundersSLAC National Accelerator LaboratoryBiological and Environmental ResearchBasic Energy SciencesNational Institute of Allergy and Infectious DiseasesInternational AIDS Vaccine InitiativeNational Institute of General Medical SciencesUniversity of California, San FranciscoBill and Melinda Gates FoundationOffice of ScienceNederlandse Organisatie voor Wetenschappelijk OnderzoekEuropean CommissionU.S. Department of EnergyEuropean Molecular Biology OrganizationNational Institutes of HealthAids Fonds
KeywordsTrimerVirologyGp41Hemagglutinin (influenza)GlycoproteinBiologyRecombinant DNAAntibodyChemistryComputational biologyGeneticsVirusGeneDimerEpitope

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.531
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.297
Teacher spread0.275 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designNot applicable
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations13
Published2024
Admission routes1
Has abstractyes

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