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Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques.
bioRxiv. 2021 Apr 10B

Abstract

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.

Authors

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Pub Type(s)

Preprint

Language

eng

PubMed ID

33851155

Citation

King, Hannah A D., et al. "Efficacy and Breadth of Adjuvanted SARS-CoV-2 Receptor-binding Domain Nanoparticle Vaccine in Macaques." BioRxiv : the Preprint Server for Biology, 2021.
King HAD, Gordon Joyce M, Naouar IE, et al. Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques. bioRxiv. 2021.
King, H. A. D., Gordon Joyce, M., Naouar, I. E., Ahmed, A., Cincotta, C. M., Subra, C., Peachman, K. K., Hack, H. H., Chen, R. E., Thomas, P. V., Chen, W. H., Sankhala, R. S., Hajduczki, A., Martinez, E. J., Peterson, C. E., Chang, W. C., Choe, M., Smith, C., Headley, J. A., ... Bolton, D. L. (2021). Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2021.04.09.439166
King HAD, et al. Efficacy and Breadth of Adjuvanted SARS-CoV-2 Receptor-binding Domain Nanoparticle Vaccine in Macaques. bioRxiv. 2021 Apr 10; PubMed PMID: 33851155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques. AU - King,Hannah A D, AU - Gordon Joyce,M, AU - Naouar,Ines Elakhal, AU - Ahmed,Aslaa, AU - Cincotta,Camila Macedo, AU - Subra,Caroline, AU - Peachman,Kristina K, AU - Hack,Holly H, AU - Chen,Rita E, AU - Thomas,Paul V, AU - Chen,Wei-Hung, AU - Sankhala,Rajeshwer S, AU - Hajduczki,Agnes, AU - Martinez,Elizabeth J, AU - Peterson,Caroline E, AU - Chang,William C, AU - Choe,Misook, AU - Smith,Clayton, AU - Headley,Jarrett A, AU - Elyard,Hanne A, AU - Cook,Anthony, AU - Anderson,Alexander, AU - Wuertz,Kathryn McGuckin, AU - Dong,Ming, AU - Swafford,Isabella, AU - Case,James B, AU - Currier,Jeffrey R, AU - Lal,Kerri G, AU - Amare,Mihret F, AU - Dussupt,Vincent, AU - Molnar,Sebastian, AU - Daye,Sharon P, AU - Zeng,Xiankun, AU - Barkei,Erica K, AU - Alfson,Kendra, AU - Staples,Hilary M, AU - Carrion,Ricardo, AU - Krebs,Shelly J, AU - Paquin-Proulx,Dominic, AU - Karasavvas,Nicos, AU - Polonis,Victoria R, AU - Jagodzinski,Linda L, AU - Vasan,Sandhya, AU - Scott,Paul T, AU - Huang,Yaoxing, AU - Nair,Manoj S, AU - Ho,David D, AU - de Val,Natalia, AU - Diamond,Michael S, AU - Lewis,Mark G, AU - Rao,Mangala, AU - Matyas,Gary R, AU - Gromowski,Gregory D, AU - Peel,Sheila A, AU - Michael,Nelson L, AU - Modjarrad,Kayvon, AU - Bolton,Diane L, Y1 - 2021/04/10/ PY - 2021/4/14/entrez PY - 2021/4/15/pubmed PY - 2021/4/15/medline JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - : 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. UR - https://www.unboundmedicine.com/medline/citation/33851155/Efficacy_and_breadth_of_adjuvanted_SARS_CoV_2_receptor_binding_domain_nanoparticle_vaccine_in_macaques_ L2 - https://doi.org/10.1101/2021.04.09.439166 DB - PRIME DP - Unbound Medicine ER -
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