Proc Natl Acad Sci U S A . A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine

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Proc Natl Acad Sci U S A


. 2020 Nov 30;202014468.
doi: 10.1073/pnas.2014468117. Online ahead of print.
A highly immunogenic and effective measles virus-based Th1-biased COVID-19 vaccine


Cindy H?rner ^{1 2} , Christoph Sch?rmann ¹ , Arne Auste ^{1 2} , Aileen Ebenig ¹ , Samada Muraleedharan ¹ , Kenneth H Dinnon 3rd ³ , Tatjana Scholz ⁴ , Maike Herrmann ⁵ , Barbara S Schnierle ⁴ , Ralph S Baric ^{3 6 7} , Michael D M?hlebach ^{8 2}



Affiliations

• PMID: 33257540
• DOI: 10.1073/pnas.2014468117

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.

Keywords: COVID-19; SARS-CoV-2; Th1 immune bias; effective immunity; measles vaccine platform.