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1.
Science ; 370(6520): 1110-1115, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33037066

RESUMO

An urgent global quest for effective therapies to prevent and treat coronavirus disease 2019 (COVID-19) is ongoing. We previously described REGN-COV2, a cocktail of two potent neutralizing antibodies (REGN10987 and REGN10933) that targets nonoverlapping epitopes on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In this report, we evaluate the in vivo efficacy of this antibody cocktail in both rhesus macaques, which may model mild disease, and golden hamsters, which may model more severe disease. We demonstrate that REGN-COV-2 can greatly reduce virus load in the lower and upper airways and decrease virus-induced pathological sequelae when administered prophylactically or therapeutically in rhesus macaques. Similarly, administration in hamsters limits weight loss and decreases lung titers and evidence of pneumonia in the lungs. Our results provide evidence of the therapeutic potential of this antibody cocktail.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Neutralizantes/uso terapêutico , COVID-19/terapia , Animais , COVID-19/prevenção & controle , Combinação de Medicamentos , Macaca mulatta , Mesocricetus
2.
Nat Med ; 26(11): 1694-1700, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32884153

RESUMO

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1-4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5-7 and nonhuman primates8-10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11-13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.


Assuntos
Adenoviridae/genética , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Adenoviridae/imunologia , Animais , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/uso terapêutico , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Cricetinae , Modelos Animais de Doenças , Feminino , Vetores Genéticos , Humanos , Masculino , Mesocricetus , SARS-CoV-2/genética , Índice de Gravidade de Doença , Vacinas Sintéticas/genética , Vacinas Sintéticas/uso terapêutico , Carga Viral
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