2641. Nirsevimab binding-site conservation in RSV F protein between 2015 and 2022: The US OUTSMART-RSV surveillance study
Bibliographic record
Abstract
Abstract Background Nirsevimab is an extended half-life monoclonal antibody that binds the prefusion conformation of RSV fusion (F) protein and has been approved for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants in the EU, Great Britain, and Canada. Global surveillance studies found that the nirsevimab binding site was highly conserved across RSV variants between 1956–2021. While RSV B F protein binding site substitutions I206M and Q209R have dominated since the 2017/2018 RSV season, both remain fully susceptible to nirsevimab. OUTSMART-RSV is a multi-year (from 2015) prospective molecular surveillance study to monitor the prevalence and distribution of RSV variants in the USA and track the emergence and susceptibility of RSV F variants to nirsevimab. Methods Nasal swabs were collected from infants and adults seeking medical attention for respiratory infection (inpatient or outpatient); RSV-positive isolates underwent next generation sequencing. Subtyping comprised analysis of the hypervariable region of the G protein. F protein polymorphisms were identified by comparing with RSV A and B reference sequences; variants with increasing prevalence were phenotypically evaluated using reverse genetics rescue and in vitro microneutralization assays. Results RSV A and B subtypes circulated with alternate frequency during OUTSMART-RSV (Figure 1), with RSV B dominant in the 2021/2022 RSV season (sequence count 509 vs 46 for RSV A; Table 1). From 2020, several additional RSV B F protein substitutions have increased in prevalence, including the S211N binding site substitution. Importantly, S211N retains full susceptibility to nirsevimab (IC50 fold change = 1.24 vs reference). Also, no new nirsevimab binding site substitutions were seen in the 2021/2022 RSV season vs previous seasons. Conclusion While I206M and Q209R substitutions in RSV B F protein continue to dominate, the S211N nirsevimab binding site substitution has increased in prevalence since the 2020-2021 season. However, similar to I206M and Q209R, S211N variants remain fully susceptible to nirsevimab. Among recent circulating RSV strains, the frequency of emergent nirsevimab escape variants continue to be rare and not persistent. Disclosures Christopher A. Morehouse, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kevin M. Tuffy, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hong Ji, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Elizabeth J. Kelly, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".