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1.
J Infect Dis ; 213(7): 1124-33, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26715676

RESUMO

The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease.


Assuntos
Anticorpos Antivirais/uso terapêutico , Ebolavirus/fisiologia , Glicoproteínas/imunologia , Doença pelo Vírus Ebola/terapia , Imunoglobulina G/uso terapêutico , Glicoproteínas de Membrana/metabolismo , Animais , Anticorpos Antivirais/economia , Análise Custo-Benefício , Ebolavirus/imunologia , Feminino , Regulação Viral da Expressão Gênica , Cobaias , Células HEK293 , Doença pelo Vírus Ebola/economia , Humanos , Imunoglobulina G/economia , Glicoproteínas de Membrana/imunologia , Ligação Proteica , Estrutura Terciária de Proteína , Ovinos , Carga Viral
2.
Antiviral Res ; 203: 105332, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35533779

RESUMO

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.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Animais , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais , COVID-19/terapia , Análise Custo-Benefício , Imunização Passiva , SARS-CoV-2 , Ovinos , Glicoproteína da Espícula de Coronavírus , Soroterapia para COVID-19
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