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Record W2998531164 · doi:10.1128/jvi.01933-19

Expression of CD40L by the ALVAC-Simian Immunodeficiency Virus Vector Abrogates T Cell Responses in Macaques

2020· article· en· W2998531164 on OpenAlexafffund
Isabela Silva de Castro, Shari N. Gordon, Jun Liu, Massimiliano Bissa, Katherine McKinnon, Hung V. Trinh, Melvin N. Doster, Luca Schifanella, Namal P. M. Liyanage, JinChao Cao, Olivia Cheng, Kathryn E. Foulds, Mario Roederer, Richard A. Koup, Xiaoying Shen, Georgia D. Tomaras, David Venzon, Donald N. Forthal, Timothy Fouts, David C. Montefiori, Jim Tartaglia, Mangala Rao, Mario Ostrowski, Genoveffa Franchini, Monica Vaccari

Bibliographic record

VenueJournal of Virology · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversity of TorontoSt. Michael's Hospital
FundersNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteArts and Humanities Research CouncilSanofi PasteurNational Science FoundationCanadian Institutes of Health ResearchHenry M. Jackson FoundationU.S. Department of DefenseSanofiOntario HIV Treatment NetworkBill and Melinda Gates FoundationSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungGovernment of Canada
KeywordsBiologyVirologySimian immunodeficiency virusImmune systemImmunologyAntibodyCytotoxic T cellCD40LentivirusT cellVirusViral diseaseIn vitroGenetics

Abstract

fetched live from OpenAlex

CD40-CD40 ligand (CD40L) interaction is crucial for inducing effective cytotoxic and humoral responses against pathogens. Because of its immunomodulatory function, CD40L has been used to enhance immune responses to vaccines, including candidate vaccines for HIV. The only successful vaccine ever tested in humans utilized a strategy combining canarypox virus-based vector (ALVAC) together with an envelope protein (gp120) adjuvanted in alum. This strategy showed limited efficacy in preventing HIV-1/SIV acquisition in humans and macaques. In both species, protection was associated with vaccine-induced antibodies against the HIV envelope and CD4 + T cell responses, including type 1 antiviral responses. In this study, we tested whether augmenting CD40L expression by coexpressing it with the ALVAC vector could increase the protective immune responses. Although coexpression of CD40L did increase humoral responses, it blunted type 1 CD4 + T cell responses against the SIV envelope protein and failed to protect macaques from viral infection.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.016
GPT teacher head0.270
Teacher spread0.255 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
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

Citations9
Published2020
Admission routes2
Has abstractyes

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