Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults
Ben Killingley, Alex J Mann, Mariya Kalinova, Alison Boyers, Niluka Goonawardane, Jie Zhou, Kate Lindsell, Samanjit S Hare, Jonathan Brown, Rebecca Frise, Emma Smith, Claire Hopkins, Nicolas Noulin, Brandon Löndt, Tom Wilkinson, Stephen Harden, Helen Mcshane, Mark Baillet, Anthony Gilbert, Michael Jacobs, Christine Charman, Priya Mande, Jonathan S Nguyen-Van-Tam, Malcolm G Semple, Robert C Read, Neil M Ferguson, Peter J Openshaw, Garth Rapeport, Wendy S Barclay, Andrew P Catchpole, Christopher Chiu
Nature Medicine, doi:10.1038/s41591-022-01780-9
oronavirus disease 2019 (COVID-19) is a complex clinical syndrome caused by SARS-CoV-2. Despite extensive research into severe disease of hospitalized patients 1 and many large studies leading to approval of vaccines and antivirals 2-4 , the global spread of SARS-CoV-2 continues and is, indeed, accelerating in many regions. Infections are typically mild or asymptomatic in younger people, but these likely drive community transmission 5 , and the detailed time course of infection and infectivity in this context has not been fully elucidated 6, 7 . Deliberate human infection of low-risk volunteers enables the exact longitudinal measurement of viral kinetics, immunological responses, transmission dynamics and duration of infectious shedding after a fixed dose of
Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults
Online content Any methods, additional references, Nature Research reporting summaries, source data, extended data, supplementary information, acknowledgements, peer review information; details of author contributions and competing interests; and statements of data and code availability are available at https://doi.org/10.1038/ s41591-022-01780-9 .
Articles
Nature MediciNe V-Spot image analyzer, with virus titer determined by calculating the average spot number and subtraction of background spot count from the negative control wells. Serum antibody assays. Serum samples were analyzed at Nexelis to determine SARS-CoV-2 anti-spike IgG concentrations by ELISA (reported as ELU ml -1 ). Neutralizing antibody titers for live SARS-CoV-2 virus (lineage Victoria/01/2020) were determined by microneutralization assay at the UK Health Security Agency and reported as the 50% neutralizing antibody titer (NT 50 ). For the microneutralization assay, lower limit of detection (LLOD) was 58, and undetectable samples were assigned a value of 29. For the spike protein IgG ELISA, LLOD was 50.2 ELU ml -1 , and undetectable samples were assigned a value of 25 ELU ml -1 . Lateral flow rapid antigen assays. LFAs were performed using the Innova SARS-CoV-2 antigen rapid quantitative test kit (BT1309) as per the manufacturer's recommendations with adaptations as follows. This commercially available kit is designed to detect the presence of the SARS-CoV-2 nucleocapsid protein through in vitro..
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