Structural and functional analysis of VYD222: a broadly neutralizing antibody against SARS-CoV-2 variants
Bibliographic record
Abstract
Extensive mutations in SARS-CoV-2 spike protein have rendered most therapeutic monoclonal antibodies (mAbs) ineffective. However, here we describe VYD222 (pemivibart), a human mAb re-engineered from ADG20 (adintrevimab), which maintains potency despite substantial virus evolution. VYD222 received FDA Emergency Use Authorization for pre-exposure prophylaxis of COVID-19 in certain immunocompromised adults and adolescents. Here we show potent neutralization of this antibody against a broad range of emerging variants, including Omicron KP.3 and KP.3.1.1. X-ray crystal structures of VYD222 complexed with the receptor-binding domains of prototype SARS-CoV-2 and Omicron BA.5 demonstrate the binding epitope spans from the receptor binding site to the conserved CR3022 site. Notably, many of the matured residues between ADG20 and VYD222 occur outside the paratopic region. Deep mutational scanning indicates that SARS-CoV-2's ability to escape VYD222 is constrained by structural compatibility and the need to maintain receptor binding. These findings provide crucial insights into the escape-resistant neutralization of VYD222 against a broad panel of clinically relevant SARS-CoV-2 variants and offer valuable guidance for risk assessment of emergent variants.
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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 | 0.000 | 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".