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Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Sampson, Alexander Thomas 
Heeney, Jonathan 
Cantoni, Diego 
Ferrari, Matteo 
Sans, Maria Suau 

Abstract

The novel coronavirus SARS-CoV-2 is the seventh identified human coronavirus. Understanding the extent of pre-existing immunity induced by seropositivity to endemic seasonal coronaviruses and the impact of cross-reactivity on COVID-19 disease progression remains a key research question in immunity to SARS-CoV-2 and the immunopathology of COVID-2019 disease. This paper describes a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth. Optimal production conditions and most readily available permissive target cell lines were determined for spike-mediated entry by each HCoV pseudotype: SARS-CoV-1, SARS-CoV-2 and HCoV-NL63 best transduced HEK293T/17 cells transfected with ACE2 and TMPRSS2, HCoV-229E and MERS-CoV preferentially entered HUH7 cells, and CHO cells were most permissive for the seasonal betacoronavirus HCoV-HKU1. Entry of ACE2 using pseudotypes was enhanced by ACE2 and TMPRSS2 expression in target cells, whilst TMPRSS2 transfection rendered HEK293T/17 cells permissive for HCoV-HKU1 and HCoV-OC43 entry. Additionally, pseudotype viruses were produced bearing additional coronavirus surface proteins, including the SARS-CoV-2 Envelope (E) and Membrane (M) proteins and HCoV-OC43/HCoV-HKU1 Haemagglutinin-Esterase (HE) proteins. This panel of lentiviral pseudotypes provides a safe, rapidly quantifiable and high-throughput tool for serological comparison of pan-coronavirus neutralizing responses; this can be used to elucidate antibody dynamics against individual coronaviruses and the effects of antibody cross-reactivity on clinical outcome following natural infection or vaccination.

Description

Keywords

Animals, Antibodies, Viral, Broadly Neutralizing Antibodies, Cell Line, Coronavirus, Coronavirus 229E, Human, Coronavirus NL63, Human, Coronavirus OC43, Human, COVID-19, Cross Reactions, Humans, Lentivirus, Middle East Respiratory Syndrome Coronavirus, Neutralization Tests, Plasmids, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Transfection, Virus Internalization, coronavirus, COVID-19, neutralization, pseudotyped virus, SARS-CoV-2

Journal Title

Viruses

Conference Name

Journal ISSN

1999-4915
1999-4915

Volume Title

13

Publisher

MDPI AG
Sponsorship
Innovate UK (971616)