Development of high titer anti-drug antibodies in a Phase 1b/2a infant clesrovimab trial are associated with RSV exposure beyond day 150.

Background: Clesrovimab is a human half-life extended mAb in phase 3 evaluation for the prevention of RSV disease in infants. ADA were observed at late time points in a phase 1b/2a study where clesrovimab was well tolerated with an extended half-life of ∼45 days.

Methods: Serum samples at days 150, 365 and 545 post-dose were assayed for ADA titers.

Analysis of the first genetic engineering attribution challenge.

The ability to identify the designer of engineered biological sequences-termed genetic engineering attribution (GEA)-would help ensure due credit for biotechnological innovation, while holding designers accountable to the communities they affect. Here, we present the results of the first Genetic Engineering Attribution Challenge, a public data-science competition to advance GEA techniques. Top-scoring teams dramatically outperformed previous models at identifying the true lab-of-origin of engineered plasmid sequences, including an increase in top-1 and top-10 accuracy of 10 percentage points.

Dataset of five years of and satellite derived chlorophyll concentrations and its spatiotemporal variability in the Rotorua Te Arawa Lakes, New Zealand.

Horizontal patchiness of water quality attributes in lakes substantially influences the ability to accurately determine an average condition of a lake from traditional in situ sampling. Monitoring programmes for lake water quality often rely on water samples from one or few locations but the assumption of representativeness is seldomly tested. Satellite observations can support environmental monitoring by detecting horizontal variability of water quality attributes over entire lakes.

Evaluating Use Cases for Human Challenge Trials in Accelerating SARS-CoV-2 Vaccine Development.

Human challenge trials (HCTs) have been proposed as a means to accelerate SARS-CoV-2 vaccine development. We identify and discuss 3 potential use cases of HCTs in the current pandemic: evaluating efficacy, converging on correlates of protection, and improving understanding of pathogenesis and the human immune response. We outline the limitations of HCTs and find that HCTs are likely to be most useful for vaccine candidates currently in preclinical stages of development.

Analysis of regulatory guidance on antidrug antibody testing for therapeutic protein products.

Therapeutic proteins have the potential to induce unwanted immune responses. The potential impact of immunogenicity on pharmacokinetics, pharmacodynamics, safety and efficacy are well established. Here, we analyze key aspects of current US FDA and EMA guidelines on the development and validation of antidrug antibody assays.