Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

Li, D.; Martinez, D. R.; Schäfer, A.; Chen, H.; Barr, M.; Sutherland, L. L.; Lee, E.; Parks, R.; Mielke, D.; Edwards, W.; Newman, A.; Bock, K. W.; Minai, M.; Nagata, B. M.; Gagne, M.; Douek, D.; DeMarco, C. T.; Denny, T. N.; Oguin, T. H.; Rountree, W.; Wang, Y.; Mansouri, K.; Edwards, R. J.; Ferrari, G.; Sempowski, G. D.; Eaton, A.; Tang, J.; Cain, D. W.; Santra, S.; Pardi, N.; Weissman, D.; Tomai, M.; Fox, C.; Moore, I. N.; Andersen, H.; Lewis, M. G.; Golding, H.; Khurana, S.; Seder, R.; Baric, R. S.; Montefiori, D. C.; Saunders, K. O.; Haynes, B. F.

doi:10.1101/2022.01.26.477915

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bioRxiv · 10.1101/2022.01.26.477915

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

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Abstract

Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected 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 NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.

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Li, D., Martinez, D. R., Schäfer, A., Chen, H., Barr, M., Sutherland, L. L., Lee, E., Parks, R., Mielke, D., Edwards, W., Newman, A., Bock, K. W., Minai, M., Nagata, B. M., Gagne, M., Douek, D., DeMarco, C. T., Denny, T. N., Oguin, T. H., Rountree, W., Wang, Y., Mansouri, K., Edwards, R. J., Ferrari, G., Sempowski, G. D., Eaton, A., Tang, J., Cain, D. W., Santra, S., Pardi, N., Weissman, D., Tomai, M., Fox, C., Moore, I. N., Andersen, H., Lewis, M. G., Golding, H., Khurana, S., Seder, R., Baric, R. S., Montefiori, D. C., Saunders, K. O., Haynes, B. F.. 2022-01-28. Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine. https://doi.org/10.1101/2022.01.26.477915

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