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

• Published in: Nature communications Vol. 13; no. 1; pp. 6309 - 15
• Main Authors: Li, Dapeng, Martinez, David R., Schäfer, Alexandra, Chen, Haiyan, Barr, Maggie, Sutherland, Laura L., Lee, Esther, Parks, Robert, Mielke, Dieter, Edwards, Whitney, Newman, Amanda, Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Gagne, Matthew, Douek, Daniel C., DeMarco, C. Todd, Denny, Thomas N., Oguin, Thomas H., Brown, Alecia, Rountree, Wes, Wang, Yunfei, Mansouri, Katayoun, Edwards, Robert J., Ferrari, Guido, Sempowski, Gregory D., Eaton, Amanda, Tang, Juanjie, Cain, Derek W., Santra, Sampa, Pardi, Norbert, Weissman, Drew, Tomai, Mark A., Fox, Christopher B., Moore, Ian N., Andersen, Hanne, Lewis, Mark G., Golding, Hana, Seder, Robert, Khurana, Surender, Baric, Ralph S., Montefiori, David C., Saunders, Kevin O., Haynes, Barton F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/51; 631/250/590/1962; 631/250/590/2293; 631/326/596/4130; 64; 64/60; 82/83; Animals; Antibodies; Antibodies, Neutralizing - chemistry; Antibodies, Viral; Coronaviruses; COVID-19; COVID-19 - prevention & control; Ferritin; Ferritins; Humanities and Social Sciences; Immunization; Infections; Mice; Mice, Inbred BALB C; multidisciplinary; Mutation; Nanoparticles; Neutralization; Neutralizing; Primates; Sarbecovirus; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome-related coronavirus; Sortase; Spike Glycoprotein, Coronavirus; Vaccines; Viral diseases; Viral Vaccines; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33985-4

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. The authors have previously demonstrated the neutralising capacity of their nanoparticle vaccine, as well as showing protection of non-human primates from SARS-CoV-2 WA-1 infection. In this work, they investigate the ability of their vaccine candidate to neutralise SARS-CoV-2 variants of concern, and protect animals from other sarbecoviruses.