Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
Proc Natl Acad Sci U S A.
2021-09;
Hannah A D King, M Gordon Joyce, Ines Lakhal-Naouar, Aslaa Ahmed, Camila Macedo Cincotta, Caroline Subra, Kristina K Peachman, Holly R Hack, Rita E Chen, Paul V Thomas, Wei-Hung Chen, Rajeshwer S Sankhala, Agnes Hajduczki, Elizabeth J Martinez, Caroline E Peterson, William C Chang, Misook Choe, Clayton Smith, Jarrett A Headley, Hanne A Elyard, Anthony Cook, Alexander Anderson, Kathryn McGuckin Wuertz, Ming Dong, Isabella Swafford, James B Case, Jeffrey R Currier, Kerri G Lal, Mihret F Amare, Vincent Dussupt, Sebastian Molnar, Sharon P Daye, Xiankun Zeng, Erica K Barkei, Kendra Alfson, Hilary M Staples, Ricardo Carrion, Shelly J Krebs, Dominic Paquin-Proulx, Nicos Karasavvas, Victoria R Polonis, Linda L Jagodzinski, Sandhya Vasan, Paul T Scott, Yaoxing Huang, Manoj S Nair, David D Ho, Natalia de Val, Michael S Diamond, Mark G Lewis, Mangala Rao, Gary R Matyas, Gregory D Gromowski, Sheila A Peel, Nelson L Michael, Kayvon Modjarrad, Diane L Bolton
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| Gene Synthesis |
RBD was attached to?H. pylori?ferritin using a GSGGGG linker followed by a short sequence (ESQVRQQFSK) derived from bullfrog ferritin (69) and synthesized by GenScript |
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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 serum neutralizing antibody titers of 14,000 to 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... More
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 serum neutralizing antibody titers of 14,000 to 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 4 d in seven of eight animals receiving 50 μg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV-like Sarbecovirus vaccine development.
SARS-CoV-2, adjuvant, macaque, nanoparticle, vaccine
