Monoclonal antibodies recognizing a putative immunodominant epitope in the hemagglutinin stalk do not enhance influenza A virus mediated fusion activity (VIR5P.1156)
Bibliographic record
Abstract
Abstract The discovery of broadly neutralizing antibodies (Abs) which bind to the conserved hemagglutinin (HA) stalk has led to renewed interest in the development of a universal influenza virus vaccine. In swine, there have been isolated reports of vaccine-induced enhancement of disease in heterologous vaccination and challenge studies. It has been suggested that Abs recognizing the HA stalk promote virus fusion activity, contributing to pathology in pigs. Given that robust data in mouse and ferret models suggests a protective role for stalk Abs, here we examined the relationship between HA-stalk binding Abs and fusion. We generated mouse monoclonal Abs C4 and C6, which recognize a previously identified minimal epitope in the HA stalk. These Abs lack hemagglutination inhibition activity and did not inhibit or enhance virus-mediated fusion in vitro.In a mouse challenge model, we assessed the consequences of pre-exposure administration of a C4/C6 cocktail. No significant differences were observed in animals receiving C4/C6 in morbidity and mortality relative to naïve and isotype controls. We also probed the sera from a cohort of individuals who received an H5N1 vaccine. Although we detected baseline levels of Abs to the minimal stalk epitope associated with increased fusion activity in swine, titers did not increase post-vaccination. Together, our data suggests that stalk Abs do not enhance virus-mediated fusion and thus should not impede progress toward a universal influenza vaccine.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".