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

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.

authors

Hörner C,Schürmann C,Auste A,Ebenig A,Muraleedharan S,Dinnon KH 3rd,Scholz T,Herrmann M,Schnierle BS,Baric RS,Mühlebach MD

doi

10.1073/pnas.2014468117

subject

Has Abstract

pub_date

2020-12-22 00:00:00

pages

32657-32666

issue

51

eissn

0027-8424

issn

1091-6490

pii

2014468117

journal_volume

117

pub_type

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