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

被引:3
作者
Findlay-Wilson, Stephen [1 ]
Easterbrook, Linda [1 ]
Smith, Sandra [2 ]
Pope, Neville [3 ]
Humphries, Gareth [4 ]
Schuhmann, Holger [4 ]
Ngabo, Didier [1 ]
Rayner, Emma [1 ]
Otter, Ashley David [1 ]
Coleman, Tom [1 ]
Hicks, Bethany [1 ]
Graham, Victoria Anne [1 ]
Halkerston, Rachel [1 ]
Apostolakis, Kostis [1 ]
Taylor, Stephen [1 ]
Fotheringham, Susan [1 ]
Horton, Amanda [1 ]
Tree, Julia Anne [1 ]
Wand, Matthew [1 ]
Hewson, Roger [1 ]
Dowall, Stuart David [1 ]
机构
[1] United Kingdom Hlth Secur Agcy UKHSA, Porton Down, Salisbury SP4 0JG, Wiltshire, England
[2] Int Therapeut Prot Ltd Australia, Longford, Tas 7301, Australia
[3] Int Therapeut Prot Ltd UK, Goleigh Farm, Selborne GU34 3SE, Hampshire, England
[4] Native Antigen Co, Langford Locks, Oxford OX5 1LH, Oxfordshire, England
关键词
SARS-CoV-2; COVID-19; Antibodies; Therapy; Development; Omicron; RECEPTOR-BINDING; MECHANISMS;
D O I
10.1016/j.antiviral.2022.105332
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 multifunctional activity.
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页数:11
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