Combination attenuation offers strategy for live-attenuated coronavirus vaccines

Vineet D. Menachery; Lisa E. Gralinski; Hugh D. Mitchell; Kenneth H. Dinnon; Sarah R. Leist; Boyd L. Yount; Eileen T. McAnarney; Rachel L. Graham; Katrina M. Waters; Ralph S. Baric

With concerns for reversion and potential virulence, a live-attenuated vaccine platform targeting 187 only NSP16 activity should be limited to only dire circumstances. One possibility is to expand 188 . CC-BY-NC-ND 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/309591 doi: bioRxiv preprint control (Fig. 6F) . Importantly, sera from dNSP16/ExoN vaccinated mice was capable of 215 neutralizing both WT SARS-CoV as well as chimeric spike virus (Fig. 6H) . While not equivalent 216 to neutralization induced by the dNSP16 mutant (Fig. 2) , the results indicate that the double 217 mutant vaccine provided robust protection from both homologous and heterologous challenge.