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A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine.

Authors :
Hörner C
Schürmann C
Auste A
Ebenig A
Muraleedharan S
Dinnon KH 3rd
Scholz T
Herrmann M
Schnierle BS
Baric RS
Mühlebach MD
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Dec 22; Vol. 117 (51), pp. 32657-32666. Date of Electronic Publication: 2020 Nov 30.
Publication Year :
2020

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 <superscript>+</superscript> and CD4 <superscript>+</superscript> 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.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2020 the Author(s). Published by PNAS.)

Details

Language :
English
ISSN :
1091-6490
Volume :
117
Issue :
51
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
33257540
Full Text :
https://doi.org/10.1073/pnas.2014468117