Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

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.

Emergence 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 Statement The 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.