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.

mRNA based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus neutralizing antibodies and mediates protection in rodents

“…These experiments showed significant reduction in replicating virus levels in the upper respiratory tract and the absence of detectable live virus in the lungs of animals upon two vaccinations with 10 μg of CVnCoV. This result is in line with previous observations in other respiratory viruses as well in SARS-CoV-2 challenge models in hamsters 30 and non-human primates 13,44 , where robust immune responses induced better protection in the lower than in the upper respiratory tract.…”

“…On day 56, four weeks after the second vaccination, all animals were challenged with 10 2 TCID 50 /dose of SARS-CoV-2 featuring D614G. While this infection dose is low compared to other studies that employed doses of 2 x 10 3 to 2 x 10 6 TCID 50 30, 31, 32, 33, 34, 35, 36 , our results show robust levels of viral replication in the upper and lower respiratory tract (Figure 4) as well as typical weight loss for this model system 30, 31, 33 (Supplementary Figure 1) in the buffer control group.…”

A measles-vectored COVID-19 vaccine induces long-term immunity and protection from SARS-CoV-2 challenge in mice

“…We successfully rescued genectically stable rMV expressing high levels of S antigen from a strong early promoter of measles virus genome. This is in contrast to recently reported MV-based COVID-19 vaccine candidates 37 . Our lead candidate MV-ATU2-SF-2P-dER exibited a high viral titer (10 6 TCID 50 ) comparable to wild-type Schwarz MV strain and was genetically stable up to 10 passages while the previously reported rMV expressing the native S in the same promoter showed impaired growth 37 .…”

“…This is in contrast to recently reported MV-based COVID-19 vaccine candidates 37 . Our lead candidate MV-ATU2-SF-2P-dER exibited a high viral titer (10 6 TCID 50 ) comparable to wild-type Schwarz MV strain and was genetically stable up to 10 passages while the previously reported rMV expressing the native S in the same promoter showed impaired growth 37 . One explaination could be that the 2P mutation helps a stable S protein expression therefore allowing rMV to grow better.…”

A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike

“…During preparation of this manuscript, Hörner et al reported an rMeV-based SARS-CoV-2 vaccine candidate (58). They inserted the full-length S gene between the H and L genes, the last two genes of the MeV genome and therefore the S protein would be expressed at a lower level.…”