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

Authors :
Aileen Ebenig
Arne Auste
Samada Muraleedharan
Barbara S. Schnierle
Ralph S. Baric
Christoph Schürmann
Cindy Hörner
Tatjana Scholz
Kenneth H. Dinnon
Michael D. Mühlebach
Maike Herrmann
Source :
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences of the United States of America
Publication Year :
2020
Publisher :
Proceedings of the National Academy of Sciences, 2020.

Abstract

Significance The COVID-19 pandemic has already caused over 1 million deaths. Therefore, effective vaccine concepts are urgently needed. In search of such a concept, we have analyzed a measles virus-based vaccine candidate targeting SARS-CoV-2. Using this well-known, safe vaccine backbone, we demonstrate here induction of functional immune responses in both arms of adaptive immunity, yielding antiviral efficacy in vivo with the desired immune bias. Consequently, no immunopathologies became evident during challenge experiments. Moreover, the candidate still induces immunity against the measles, recognized as a looming second menace, when countries are forced to stop routine vaccination campaigns in the face of COVID-19. Thus, a bivalent measles-based COVID-19 vaccine could be the solution for two significant public health threats.<br />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.

Details

Language :
English
ISSN :
10916490 and 00278424
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....c8cb5cbbbeeef79bd900acf3d0c2594e
Full Text :
https://doi.org/10.1073/pnas.2014468117