Biology subjects

Farmer, J.

Publications and source records attributed to Farmer, J..

2 recordsLinked to original sources

bioRxiv2021

SARS-CoV-2 Spike Pseudoviruses: A Useful tool to study virus entry and address emerging neutralization escape phenotypes

SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially, variants of concern (VOC) are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests the SARS-CoV-2 neutralizing anti-body levels as a good correlate of vaccine mediated protection. However, currently used BSL3 based virus micro-neutralization (MN) assays are more laborious, time consuming and expensive, underscoring the need for BSL2 based, cost effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL2 pseudovirus based neutralization assay (PBNA) in cells expressing Angiotensin Converting Enzyme-2 (ACE2) receptor for SARS-CoV-2. The assay is reproducible (R2=0.96), demonstrates a good dynamic range and high sensitivity. Our data suggests that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 RSA and B1.1.7 UK VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 Spike Pseudovirus based neutralization assays for VOC would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.

microbiology↗

bioRxiv2021

The responsiveness of gait and balance outcomes to disease progression in Friedreich ataxia

ObjectiveTo identify gait and balance measures that are responsive to change during the timeline of a clinical trial in Friedreich ataxia (FRDA) we administered a battery of potential measures three times over a 12-month period. MethodsSixty-one ambulant individuals with FRDA underwent assessment of gait and balance at baseline, six months and 12 months. Outcomes included: GAITRite(R) spatiotemporal gait parameters; Biodex Balance System Postural Stability Test (PST) and Limits of Stability; Berg Balance Scale (BBS); Timed 25 Foot Walk Test; Dynamic Gait Index (DGI); SenseWear MF Armband step and energy activity; and the Friedreich Ataxia Rating Scale Upright Stability Subscale (FARS USS). The standardised response mean (SRM) or correlation coefficients were reported as effect size indices for comparison of internal responsiveness. Internal responsiveness was also analysed in subgroups. ResultsSenseWear Armband daily step count had the largest effect size of all the variables over six months (SRM=-0.615), while the PST medial-lateral index had the largest effect size (SRM=0.829) over 12 months. The FARS USS (SRM=0.824) and BBS (SRM=-0.720) were the only outcomes able to detect change over 12 months in all subgroups. The DGI was the most responsive outcome in children, detecting a mean change of -2.59 (95% CI -3.52 to -1.66, p<0.001, SRM=-1.429). ConclusionsThe FARS USS and BBS are highly responsive and can detect change in a wide range of ambulant individuals with FRDA. However, therapeutic effects in children may be best measured by the DGI.

neuroscience↗