Development of a cost-effective ovine antibody-based therapy against SARS-CoV-2 infection and contribution of antibodies specific to the spike subunit proteins.


Journal

Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699

Informations de publication

Date de publication:
07 2022
Historique:
received: 20 12 2021
revised: 29 04 2022
accepted: 03 05 2022
pubmed: 10 5 2022
medline: 11 6 2022
entrez: 9 5 2022
Statut: ppublish

Résumé

Antibodies against SARS-CoV-2 are important to generate protective immunity, with convalescent plasma one of the first therapies approved. An alternative source of polyclonal antibodies suitable for upscaling would be more amendable to regulatory approval and widespread use. In this study, sheep were immunised with SARS-CoV-2 whole spike protein or one of the subunit proteins: S1 and S2. Once substantial antibody titres were generated, plasma was collected and samples pooled for each antigen. Non-specific antibodies were removed via affinity-purification to yield candidate products for testing in a hamster model of SARS-CoV-2 infection. Affinity-purified polyclonal antibodies to whole spike, S1 and S2 proteins were evaluated for in vitro for neutralising activity against SARS-CoV-2 Wuhan-like virus (Australia/VIC01/2020) and a recent variant of concern, B.1.1.529 BA.1 (Omicron), antibody-binding, complement fixation and phagocytosis assays were also performed. All antibody preparations demonstrated an effect against SARS-CoV-2 disease in the hamster model of challenge, with those raised against the S2 subunit providing the most promise. A rapid, cost-effective therapy for COVID-19 was developed which provides a source of highly active immunoglobulin specific to SARS-CoV-2 with multi-functional activity.

Identifiants

pubmed: 35533779
pii: S0166-3542(22)00101-2
doi: 10.1016/j.antiviral.2022.105332
pmc: PMC9075985
pii:
doi:

Substances chimiques

Antibodies, Neutralizing 0
Antibodies, Viral 0
Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105332

Subventions

Organisme : Medical Research Council
ID : MC_PC_19077
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.

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Auteurs

Stephen Findlay-Wilson (S)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Linda Easterbrook (L)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Sandra Smith (S)

International Therapeutic Proteins Ltd (Australia), Longford, Tasmania, 7301, Australia.

Neville Pope (N)

International Therapeutic Proteins Ltd (UK), Goleigh Farm, Selborne, Hampshire, GU34 3SE, UK.

Gareth Humphries (G)

Native Antigen Company, Langford Locks, Kidlington, Oxford, OX5 1LH, UK.

Holger Schuhmann (H)

Native Antigen Company, Langford Locks, Kidlington, Oxford, OX5 1LH, UK.

Didier Ngabo (D)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Emma Rayner (E)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Ashley David Otter (AD)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Tom Coleman (T)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Bethany Hicks (B)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Victoria Anne Graham (VA)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Rachel Halkerston (R)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Kostis Apostolakis (K)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Stephen Taylor (S)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Susan Fotheringham (S)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Amanda Horton (A)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Julia Anne Tree (JA)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Matthew Wand (M)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Roger Hewson (R)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK.

Stuart David Dowall (SD)

United Kingdom Health Security Agency (UKHSA), Porton Down, Salisbury, Wiltshire, SP4 0JG, UK. Electronic address: stuart.dowall@phe.gov.uk.

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Classifications MeSH