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Record W3080643008 · doi:10.1172/jci138728

Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection

2020· article· en· W3080643008 on OpenAlexafffund
Hongzhao Li, Robert W. Omange, Binhua Liang, Nikki Toledo, Hai Yan, Lewis R. Liu, Dane Schalk, José Crecente‐Campo, Tamara G. Dacoba, Andrew B. Lambe, So‐Yon Lim, Lin Li, Mohammad Abul Kashem, Yanmin Wan, Jorge F. Correia‐Pinto, Michael S. Seaman, Xiaoqing Liu, Robert Balshaw, Qingsheng Li, Nancy Schultz‐Darken, Marı́a José Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Bibliographic record

VenueJournal of Clinical Investigation · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune responses and vaccinations
Canadian institutionsGeorge & Fay Yee Centre for Healthcare InnovationCenterLine (Canada)Public Health Agency of CanadaUniversity of Manitoba
FundersNational Institute of Allergy and Infectious DiseasesNIH Office of the DirectorCanadian Institutes of Health ResearchPublic Health Agency of CanadaNational Institutes of HealthNational Center for Research ResourcesPublic Health AgencyUniversity of Wisconsin-Madison
KeywordsProteaseVirologyCleavage (geology)MedicineBiologyMicrobiologyEnzymeBiochemistry

Abstract

fetched live from OpenAlex

After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with vaccine efficacy. The PCS vaccine did not induce immune activation or inflammation known to be associated with increased susceptibility to HIV infection. Machine learning analyses revealed that the immune microenvironment generated by the PCS vaccine was predictive of vaccine efficacy. Our study demonstrates, for the first time to our knowledge, that a vaccine which targets only viral maturation, but lacks full-length Env and Gag immunogens, can prevent intravaginal infection in a stringent macaque/SIV challenge model. Targeting HIV maturation thus offers a potentially novel approach to developing an effective HIV vaccine.

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)0.001
metaresearch head score (Gemma)0.007
Version: codex-gemma-dda1882f352aValidation 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 score0.235
Threshold uncertainty score0.875

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.007
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)0.0000.000

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 head0.064
GPT teacher head0.350
Teacher spread0.286 · 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.

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

Citations13
Published2020
Admission routes2
Has abstractyes

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