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

被引:46
作者
King, Hannah A. D. [1 ,2 ,3 ]
Joyce, M. Gordon [2 ,3 ]
Naouar, Ines Elakhal [3 ,4 ]
Ahmed, Aslaa [5 ]
Cincotta, Camila Macedo [3 ,4 ]
Subra, Caroline [1 ,2 ,3 ]
Peachman, Kristina K. [4 ]
Hack, Holly H. [3 ,4 ]
Chen, Rita E. [6 ,7 ]
Thomas, Paul, V [2 ,3 ]
Chen, Wei-Hung [2 ,3 ]
Sankhala, Rajeshwer S. [2 ,3 ]
Hajduczki, Agnes [2 ,3 ]
Martinez, Elizabeth J. [2 ,3 ]
Peterson, Caroline E. [2 ,3 ]
Chang, William C. [2 ,3 ]
Choe, Misook [2 ,3 ]
Smith, Clayton [8 ]
Headley, Jarrett A. [2 ,3 ]
Elyard, Hanne A. [9 ]
Cook, Anthony [9 ]
Anderson, Alexander [1 ,2 ,3 ]
Wuertz, Kathryn McGuckin [1 ]
Dong, Ming [1 ,2 ,3 ]
Swafford, Isabella [1 ,2 ,3 ]
Case, James B. [6 ]
Currier, Jeffrey R. [5 ]
Lal, Kerri G. [1 ,2 ,3 ]
Amare, Mihret F. [2 ,3 ]
Dussupt, Vincent [1 ,2 ,3 ]
Molnar, Sebastian [1 ,2 ,3 ]
Daye, Sharon P. [10 ]
Zeng, Xiankun [11 ]
Barkei, Erica K. [12 ]
Alfson, Kendra [13 ]
Staples, Hilary M. [13 ]
Carrion, Ricardo [13 ]
Krebs, Shelly J. [1 ,2 ,3 ]
Paquin-Proulx, Dominic [1 ,2 ,3 ]
Karasavvas, Nicos [3 ,4 ]
Polonis, Victoria R. [1 ]
Jagodzinski, Linda L. [4 ]
Vasan, Sandhya [1 ,2 ,3 ]
Scott, Paul T. [2 ]
Huang, Yaoxing [14 ]
Nair, Manoj S. [14 ]
Ho, David D. [14 ]
de Val, Natalia [8 ]
Diamond, Michael S. [6 ,7 ,15 ]
Lewis, Mark G. [9 ]
机构
[1] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA
[2] Walter Reed Army Inst Res, Emerging Infect Dis Branch, Silver Spring, MD 20910 USA
[3] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA
[4] Walter Reed Army Inst Res, Diagnost & Countermeasures Branch, Silver Spring, MD 20910 USA
[5] Walter Reed Army Inst Res, Viral Dis Branch, Silver Spring, MD 20910 USA
[6] Washington Univ, Dept Med, St Louis, MO 63130 USA
[7] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63130 USA
[8] NCI, Ctr Mol Microscopy, Ctr Canc Res, NIH, Frederick, MD 21702 USA
[9] BIOQUAL Inc, Rockville, MD 20850 USA
[10] Walter Reed Army Inst Res, Ctr Infect Dis Res, Silver Spring, MD 20910 USA
[11] US Army Med Res Inst Infect Dis, Div Pathol, Frederick, MD 21702 USA
[12] Walter Reed Army Inst Res, Vet Pathol Branch, Silver Spring, MD 20910 USA
[13] Texas Biomed Res Inst, Dis Intervent & Prevent, San Antonio, TX 78227 USA
[14] Columbia Univ, Aaron Diamond AIDS Res Ctr, Vagelos Coll Phys & Surg, New York, NY 10032 USA
[15] Washington Univ, Dept Mol Microbiol, St Louis, MO 63130 USA
关键词
SARS-CoV-2; vaccine; macaque; nanoparticle; adjuvant; MONOPHOSPHORYL-LIPID-A; NEUTRALIZING ANTIBODY; SPIKE; MECHANISMS; PROTECTION; INFECTION; RESPONSES; ROBUST;
D O I
10.1073/pnas.2106433118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 mu g 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.
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页数:11
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