Broad-Spectrum Antiviral Activity of Nucleic Acid-Based Antiviral Agents Against Avian and Seasonal Influenza Viruses
Bibliographic record
Abstract
The increasing prevalence of influenza viruses resistant to antiviral drugs such as amantadine and oseltamivir undermines our ability to defend against future influenza pandemics. There is an urgent need to develop novel antiviral agents which are robust and offer broad-spectrum protection against the ever changing influenza viruses. The objective of this study is to evaluate the in vivo antiviral efficacy nucleic acid-based immunomodulators such as Poly ICLC (synthetic ds RNA) and oligonucleotides containing unmethylated CpG using a mouse lethal infection model with influenza A/PR/8/34 (H1N1) and/or with the highly pathogenic avian influenza H5N1 (HPAI) viruses. Groups of BALB/c mice were pre-treated intranasally with 1 or 2 doses of liposome-encapsulated Poly ICLC (LE-Poly ICLC, 20 μg/dose/mouse) or with CpG (5 μg/dose/mouse) oligonucleotides. At various times post pre-treatment, the animals were challenged intranasally with multiple doses of influenza A/PR/8/34 or with HPAI viruses, and survival rates of control and pre-treated mice were compared at day 14 post infection. Pre-treatment with liposome-encapsulated Poly ICLC provided complete protection against 10 LD50 influenzaA/PR/8/34 and 1 LD50 dose of HPIA virus. When the challenge dose of HPIA was increased to 4 LD50, the protection provided by LE-Poly ICLC was 63–75% (p < 0.001 vs control), with all control mice succumbed to the infection. Pre-treatment with CpG oligonucleotides provided complete protection to mice against 5 LD50 influenza A/PR/8/34. The window of protection (the time interval between drug pretreatment and virus challenge) was 21 days for LE-Poly ICLC and 4 days for CpG oligonucleotides, respectively. RT-PCR analyses of mouse lung tissues from LE-Poly ICLC treated mice showed activation of toll-like receptor-3 pathway, and induction of cytokines including IL 1-α, -β, IFN-γ, TNF-α, among others. Collectively, these results suggest that LE-Poly ICLC can provide broad-spectrum protection and may have an important role in protecting against avian or seasonal influenza infections.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".