SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness.
Kizzmekia S CorbettDarin K EdwardsSarah R LeistOlubukola M AbionaSeyhan Boyoglu-BarnumRebecca A GillespieSunny HimansuAlexandra SchäferCynthia T ZiwawoAnthony T DiPiazzaKenneth H Dinnon IiiSayda M ElbashirChristine A ShawAngela WoodsEthan J FritchDavid R MartinezKevin W BockMahnaz MinaiBianca M NagataGeoffrey B HutchinsonKai WuCarole HenryKapil BahlDario Garcia-DominguezLingZhi MaIsabella RenziWing-Pui KongStephen D SchmidtLingshu WangYi ZhangEmily PhungLauren A ChangRebecca J LoomisNedim Emil AltarasElisabeth NarayananMihir MetkarVlad PresnyakCuiping LiuMark K LouderWei ShiKwanyee LeungEun Sung YangAnde WestKendra L GullyLaura J StevensNianshuang WangDaniel WrappNicole A Doria-RoseGuillaume Stewart-JonesHamilton BennettGabriela S AlvaradoMartha C NasonTracy J RuckwardtJason S MclellanMark R DenisonJames D ChappellIan N MooreKaitlyn M MorabitoJohn R MascolaRalph S BaricAndrea CarfiBarney S GrahamPublished in: Nature (2020)
A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutations that stabilize Betacoronavirus spike proteins in the prefusion state, improving their expression and increasing immunogenicity1. This principle has been applied to design mRNA-1273, an mRNA vaccine that encodes a SARS-CoV-2 spike protein that is stabilized in the prefusion conformation. Here we show that mRNA-1273 induces potent neutralizing antibody responses to both wild-type (D614) and D614G mutant2 SARS-CoV-2 as well as CD8+ T cell responses, and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a phase III trial to evaluate its efficacy.