Author:
King Hannah A. D.,Gordon Joyce M.,Naouar Ines Elakhal,Ahmed Aslaa,Cincotta Camila Macedo,Subra Caroline,Peachman Kristina K.,Hack Holly H.,Chen Rita E.,Thomas Paul V.,Chen Wei-Hung,Sankhala Rajeshwer S.,Hajduczki Agnes,Martinez Elizabeth J.,Peterson Caroline E.,Chang William C.,Choe Misook,Smith Clayton,Headley Jarrett A.,Elyard Hanne A.,Cook Anthony,Anderson Alexander,Wuertz Kathryn McGuckin,Dong Ming,Swafford Isabella,Case James B.,Currier Jeffrey R.,Lal Kerri G.,Amare Mihret F.,Dussupt Vincent,Molnar Sebastian,Daye Sharon P.,Zeng Xiankun,Barkei Erica K.,Alfson Kendra,Staples Hilary M.,Carrion Ricardo,Krebs Shelly J.,Paquin-Proulx Dominic,Karasavvas Nicos,Polonis Victoria R.,Jagodzinski Linda L.,Vasan Sandhya,Scott Paul T.,Huang Yaoxing,Nair Manoj S.,Ho David D.,de Val Natalia,Diamond Michael S.,Lewis Mark G.,Rao Mangala,Matyas Gary R.,Gromowski Gregory D.,Peel Sheila A.,Michael Nelson L.,Modjarrad Kayvon,Bolton Diane L.
Abstract
ABSTRACTEmergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 µg RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only ∼2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development.Significance StatementThe emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.
Publisher
Cold Spring Harbor Laboratory