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Clues to finding correlates of risk/protection for HIV-1 vaccines

2017· preprint· en· W4251180468 on OpenAlexaff
Marian P. Laderoute

Bibliographic record

VenueF1000Research · 2017
Typepreprint
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsCommunications Research Centre Canada
Fundersnot available
KeywordsVaccinationVaccine trialImmunologyHIV vaccineMechanism (biology)VirologyClinical trialMedicineBiologyHuman immunodeficiency virus (HIV)AntibodyBioinformatics

Abstract

fetched live from OpenAlex

Almost a decade later, we still do not understand why in the STEP trial (2008), males with pre-existing antibodies to the Ad5 vector were associated with initial increased risk of HIV-1 acquisition. Similarly, we have little conclusive evidence of why in the RV144 trial (2009), vaccination with the ALVAC-HIV/AIDSVAX B/E was associated initially with almost a 60% vaccine efficacy at year one, which waned over 42 months to 31.2%, and where females were more protected than males. Based on the literature and trial outcomes, it was deduced that the elusive correlate of risk/protection may pertain to a novel, potent, innate protector mechanism launched by alternatively activated macrophages, which is probably induced by viruses and female steroid hormones. It was also suggested this mechanism was not likely amenable to discovery using standard or traditional approaches. A plausible, candidate mechanism was identified with these characteristics, namely the production of human endogenous retrovirus–K102 (HERV-K102) particles, which occurs in, and generates, foamy macrophages in vitro . Accumulating clinical, biological and phylogenetic evidence supports its role in the antagonism of HIV-1 replication and/or in the prevention of HIV-1 acquisition. Thus, it will be important to examine HERV-K102 particle production, increased integration and envelop antibody production as candidate correlates of protection in HIV-1 vaccine trials, as well as in HIV-1 highly exposed seronegative cohorts and elite controllers. The results of such efforts may have important ramifications for the HIV-1 cure in addition to vaccines.

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)0.009
metaresearch head score (Gemma)0.022
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.046

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0090.022
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0020.002
Science and technology studies0.0010.001
Scholarly communication0.0040.003
Open science0.0010.001
Research integrity0.0010.004
Insufficient payload (model declined to judge)0.0060.002

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 head0.067
GPT teacher head0.370
Teacher spread0.303 · 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 designObservational
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

Citations0
Published2017
Admission routes1
Has abstractyes

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