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Science . Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice

tetano

Editor, Senior Moderator
Science


. 2021 Jan 12;eabf6840.
doi: 10.1126/science.abf6840. Online ahead of print.
Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice


Alexander A Cohen[SUP] 1 [/SUP], Priyanthi N P Gnanapragasam[SUP] 1 [/SUP], Yu E Lee[SUP] 1 [/SUP], Pauline R Hoffman[SUP] 1 [/SUP], Susan Ou[SUP] 1 [/SUP], Leesa M Kakutani[SUP] 1 [/SUP], Jennifer R Keeffe[SUP] 1 [/SUP], Hung-Jen Wu[SUP] 2 [/SUP], Mark Howarth[SUP] 2 [/SUP], Anthony P West[SUP] 1 [/SUP], Christopher O Barnes[SUP] 1 [/SUP], Michel C Nussenzweig[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 4 [/SUP]



Affiliations

Abstract

Protection against SARS-CoV-2 and SARS-related emergent zoonotic coronaviruses is urgently needed. We made homotypic nanoparticles displaying the receptor-binding domain (RBD) of SARS-CoV-2 or co-displaying SARS-CoV-2 RBD along with RBDs from animal betacoronaviruses that represent threats to humans (mosaic nanoparticles; 4-8 distinct RBDs). Mice immunized with RBD-nanoparticles, but not soluble antigen, elicited cross-reactive binding and neutralization responses. Mosaic-RBD-nanoparticles elicited antibodies with superior cross-reactive recognition of heterologous RBDs compared to sera from immunizations with homotypic SARS-CoV-2-RBD-nanoparticles or COVID-19 convalescent human plasmas. Moreover, sera from mosaic-RBD-immunized mice neutralized heterologous pseudotyped coronaviruses equivalently or better after priming than sera from homotypic SARS-CoV-2-RBD-nanoparticle immunizations, demonstrating no immunogenicity loss against particular RBDs resulting from co-display. A single immunization with mosaic-RBD-nanoparticles provides a potential strategy to simultaneously protect against SARS-CoV-2 and emerging zoonotic coronaviruses.
 
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