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Proc Natl Acad Sci U S A ; 117(51): 32657-32666, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33257540

RESUMO

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8+ and CD4+ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Vírus do Sarampo/imunologia , SARS-CoV-2/imunologia , Células Th1/imunologia , Animais , Anticorpos Antivirais/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/genética , Humanos , Vacina contra Sarampo/genética , Vacina contra Sarampo/imunologia , Vírus do Sarampo/genética , Camundongos , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T/imunologia
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