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Record W2898556977 · doi:10.1101/454769

Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates

2018· preprint· en· W2898556977 on OpenAlexafffund
Matthias Pauthner, Joseph P. Nkolola, Colin Havenar‐Daughton, Ben Murrell, Samantha Reiss, Raiza Bastidas, Jérémie Prévost, Rebecca Nedellec, Benjamin von Bredow, Peter Abbink, Christopher A. Cottrell, Daniel W. Kulp, Talar Tokatlian, Bartek Nogal, Matteo Bianchi, Hui Li, Jeong Hyun Lee, Salvatore T. Butera, David T. Evans, Lars Hangartner, Andrés Finzi, Ian A. Wilson, Rich T. Wyatt, Darrell J. Irvine, William R. Schief, Andrew B. Ward, Rogier W. Sanders, Shane Crotty, George M. Shaw, Dan H. Barouch, Dennis R. Burton

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersCanadian Institutes of Health ResearchCenter for AIDS Research, University of WashingtonUniversity of California, San DiegoNational Institutes of HealthInternational AIDS Vaccine InitiativeNational Institute of Allergy and Infectious DiseasesBill and Melinda Gates Foundation
KeywordsVirologyTiterSimianVaccinationSimian immunodeficiency virusAntibody-dependent cell-mediated cytotoxicityImmunologyAntibodyNeutralizing antibodyVirusBiologyRecombinant DNAAntibody titerMedicineGeneMonoclonal antibody

Abstract

fetched live from OpenAlex

SUMMARY Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (Tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection following vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers from the BG 505 HIV isolate. Repeat intrarectal challenge with homologous Tier 2 SHIVBG 505 led to rapid infection in unimmunized and low-titer animals. In contrast, high-titer animals demonstrated protection that was gradually lost as nAb titers waned over weeks to months. From these results, we determined that an autologous serum ID 50 nAb titer of ~1:500 was required to afford over 90% protection from medium-dose SHIV infection. We further identified autologous nAb titers, but not ADCC or T cell activity, as strong correlates of protection. These results provide proof-of-concept that Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing Tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

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 score0.007

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)0.0020.000

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 head0.023
GPT teacher head0.254
Teacher spread0.230 · 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

Citations1
Published2018
Admission routes2
Has abstractyes

Explore more

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