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Record W4394804648 · doi:10.1101/2024.04.12.589199

Unleashing the Immune Arsenal: Development of Broad-spectrum Multiepitope Bluetongue Vaccine Targeting Conserved T Cell Epitopes of Structural Proteins

2024· preprint· en· W4394804648 on OpenAlexafffund
Harish Babu Kolla, Anuj Kumar, Mansi Dutt, Roopa Hebbandi Nanjunadappa, Karam Pal Singh, Peter Mertens, David J. Kelvin, Channakeshava Sokke Umeshappa

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldAgricultural and Biological Sciences
TopicVector-Borne Animal Diseases
Canadian institutionsIzaak Walton Killam Health CentreDalhousie University
FundersFaculty of Medicine, Dalhousie UniversityCanadian Institutes of Health ResearchDalhousie UniversityCanada Research Chairs
KeywordsEpitopeImmunogenicityVirologyBiologyAntigenImmune systemInnate immune systemVirusImmunology

Abstract

fetched live from OpenAlex

Bluetongue (BT) is a severe arboviral disease affecting sheep, cows, and other wild ruminants, caused by the Bluetongue virus (BTV). The virus has evolved into over 32 serotypes, rendering existing vaccines less effective. While the structural proteins of this virus represent promising targets for vaccine development, they unfortunately exhibit high amino acid polymorphism and are laden with numerous inhibitory epitopes. However, certain structural proteins such as VP1 and VP7 are highly conserved and may contain epitopes capable of triggering cross-reactive cell-mediated immunity (CMI). In this study, we identified highly conserved MHC-I and -II-restricted T cell epitopes within VP1, VP5, and VP7 BTV proteins and designed multiepitope vaccine constructs using an in silico immunoinformatics pipeline for both laboratory mouse and bovine natural systems. The conserved epitopes utilized in the vaccines are highly antigenic, non-allergenic, non-toxic, and predicted to be capable of inducing IFN-𝛾. Both mouse and bovine vaccines were tethered with Toll-like receptor (TLR)-4-agonist adjuvants, beta-defensin 2–50 S ribosomal unit to stimulate innate immunity for the CMI development. Protein-protein docking analysis suggested favorable binding affinities between the vaccine constructs and TLR4, while 100-nanosecond molecular dynamics simulations supported the structural stability of the complexes. Although these computational findings are promising, all results require experimental validation. Future in vitro and in vivo studies are essential to confirm the immunogenicity, safety, and protective efficacy of the proposed vaccine candidates in target species.

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)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.344
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.001
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 head0.013
GPT teacher head0.204
Teacher spread0.190 · 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 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

Citations0
Published2024
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicVector-Borne Animal DiseasesFrench-language works237,207