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Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine.

Dapeng LiDavid R MartinezAlexandra SchaeferHaiyan ChenMaggie BarrLaura L SutherlandEsther LeeRobert ParksDieter MielkeWhitney EdwardsAmanda NewmanKevin W BockMahnaz MinaiBianca M NagataMatthew GagneDaniel C DouekC Todd DeMarcoThomas N DennyThomas H OguinAlecia BrownWes RountreeYunfei WangKatayoun MansouriRobert J EdwardsGuido FerrariGregory D SempowskiAmanda EatonJuanjie TangDerek W CainSampa SantraNorbert PardiDrew WeissmanMark A TomaiChristopher B FoxIan N MooreHanne A ElyardMark G LewisHana GoldingRobert A SederSurender KhuranaRalph S BaricDavid C MontefioriKevin O SaundersBarton F Haynes
Published in: Nature communications (2022)
Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.
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