A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.
Proc Natl Acad Sci U S A
; 117(51): 32657-32666, 2020 12 22.
Article
em En
| MEDLINE
| ID: mdl-33257540
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
4_covid_19
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4_measles
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4_pneumonia
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6_other_respiratory_diseases
Assunto principal:
Células Th1
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Vacinas contra COVID-19
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SARS-CoV-2
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COVID-19
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Vírus do Sarampo
Limite:
Animals
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Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha