AAV-Vectored Expression of Marburg Virus–Neutralizing Antibody MR191 Provides Complete Protection From Challenge in a Guinea Pig Model
Bibliographic record
Abstract
Although there are no approved countermeasures available to prevent or treat disease caused by Marburg virus (MARV), potently neutralizing monoclonal antibodies (mAbs) derived from B cells of human survivors have been identified. One such mAb, MR191, has been shown to provide complete protection against MARV in nonhuman primates. We previously demonstrated that prophylactic administration of an adeno-associated virus (AAV) expressing MR191 protected mice from MARV. Here, we modified the AAV-MR191 coding sequence to enhance efficacy and reevaluated protection in a guinea pig model. Remarkably, 4 different variants of AAV-MR191 provided complete protection against MARV, despite administration 90 days prior to challenge. Based on superior expression kinetics, AAV-MR191-io2, was selected for evaluation in a dose-reduction experiment. The highest dose provided 100% protection, while a lower dose provided ∼88% protection. These data confirm the efficacy of AAV-mediated expression of MR191 and support the further development of this promising MARV countermeasure.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".