tetano
Editor, Senior Moderator
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[SUP] 1 2 [/SUP], Christoph Sch?rmann[SUP] 1 [/SUP], Arne Auste[SUP] 1 2 [/SUP], Aileen Ebenig[SUP] 1 [/SUP], Samada Muraleedharan[SUP] 1 [/SUP], Kenneth H Dinnon 3rd[SUP] 3 [/SUP], Tatjana Scholz[SUP] 4 [/SUP], Maike Herrmann[SUP] 5 [/SUP], Barbara S Schnierle[SUP] 4 [/SUP], Ralph S Baric[SUP] 3 6 7 [/SUP], Michael D M?hlebach[SUP] 8 2 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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.
. 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[SUP] 1 2 [/SUP], Christoph Sch?rmann[SUP] 1 [/SUP], Arne Auste[SUP] 1 2 [/SUP], Aileen Ebenig[SUP] 1 [/SUP], Samada Muraleedharan[SUP] 1 [/SUP], Kenneth H Dinnon 3rd[SUP] 3 [/SUP], Tatjana Scholz[SUP] 4 [/SUP], Maike Herrmann[SUP] 5 [/SUP], Barbara S Schnierle[SUP] 4 [/SUP], Ralph S Baric[SUP] 3 6 7 [/SUP], Michael D M?hlebach[SUP] 8 2 [/SUP]
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[SUP]+[/SUP] and CD4[SUP]+[/SUP] 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.