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.
Competing Interest Statement
B.F.H. and K.O.S. have filed US patents regarding the nanoparticle vaccine, M.A.T. and the 3M company have US patents filed on 3M-052, and C.B.F. and IDRI have filed a patent on the formulation of 3M-052-AF and 3M-052-AF + Alum. The 3M company had no role in the execution of the study, data collection or data interpretation. D.W. is named on US patents that describe the use of nucleoside-modified mRNA as a platform to deliver therapeutic proteins. D.W. and N.P. are also named on a US patent describing the use of nucleoside-modified mRNA in lipid nanoparticles as a vaccine platform. All other authors declare no competing interests.
