Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses

Bjorkman, P. J.; Cohen, A. A.; Gnanapragasam, P. N. P.; Lee, Y. E.; Ou, S.; Kakutani, L. M.; Keeffe, J. R.; Barnes, C. O.; Nussenzweig, M. C.

doi:10.1101/2020.11.17.387092

bioRxiv · 10.1101/2020.11.17.387092

Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses

Bjorkman, P. J.·Cohen, A. A.·Gnanapragasam, P. N. P.·Lee, Y. E.·Ou, S.·Kakutani, L. M.·Keeffe, J. R.·Barnes, C. O.·Nussenzweig, M. C.

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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. One sentence summaryNanoparticle strategy for pan-sarbecovirus vaccine 125-character summary for online ToCImmunizing with nanoparticles displaying diverse coronavirus RBDs elicits cross-reactive and neutralizing antibody responses.

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Bjorkman, P. J., Cohen, A. A., Gnanapragasam, P. N. P., Lee, Y. E., Ou, S., Kakutani, L. M., Keeffe, J. R., Barnes, C. O., Nussenzweig, M. C.. 2020-11-17. Mosaic RBD nanoparticles elicit neutralizing antibodies against SARS-CoV-2 and zoonotic coronaviruses. https://doi.org/10.1101/2020.11.17.387092

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