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

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.

Funding: This work was supported by funds from the State of North Carolina with funds from the federal CARES Act; NIH, NIAID, DAIDS grant AI142596 (B.F.H.), AI158571 (B.F.H.), UC6-AI058607, G20-AI167200 (G.D.S.); the Ting Tsung & Wei Fong Chao Foundation (B.F.H.); Hanna H Gray Fellowship from the Howard Hughes Medical Institute and a Postdoctoral Enrichment Award from the Burroughs Wellcome Fund (D.R.M.).

Declaration of Interests: 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.

Ethics Approval Statement: The macaques study protocol and all veterinarian procedures were approved by the Bioqual IACUC per a memorandum of understanding with the Duke IACUC, and were performed based on standard operating procedures. Macaques studied were housed and maintained in an Association for Assessment and Accreditation of Laboratory Animal Care-accredited institution in accordance with the principles of the National Institutes of Health. All studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health in BIOQUAL (Rockville, MD). BIOQUAL is fully accredited by AAALAC and through OLAW, Assurance Number A-3086. The mice study was carried out in accordance with the recommendations for care and use of animals by the Office of Laboratory Animal Welfare (OLAW), National Institutes of Health and the Institutional Animal Care and Use Committee (IACUC) of University of North Carolina (UNC permit no. A-3410-01).