@article{7473cedd271b4a9e98fedada7074c8c2,
title = "A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates",
abstract = "The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (TH1)-biased CD4 TH response and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.",
author = "Joyce, {M. Gordon} and King, {Hannah A.D.} and Ines Elakhal-Naouar and Aslaa Ahmed and Peachman, {Kristina K.} and Cincotta, {Camila Macedo} and Caroline Subra and Chen, {Rita E.} and Thomas, {Paul V.} and Chen, {Wei Hung} and Sankhala, {Rajeshwer S.} and Agnes Hajduczki and Martinez, {Elizabeth J.} and Peterson, {Caroline E.} and Chang, {William C.} and Misook Choe and Clayton Smith and Lee, {Parker J.} and Headley, {Jarrett A.} and Taddese, {Mekdi G.} and Elyard, {Hanne A.} and Anthony Cook and Alexander Anderson and {McGuckin Wuertz}, Kathryn and Ming Dong and Isabella Swafford and Case, {James Brett} and Currier, {Jeffrey R.} and Lal, {Kerri G.} and Sebastian Molnar and Nair, {Manoj S.} and Vincent Dussupt and Daye, {Sharon P.} and Xiankun Zeng and Barkei, {Erica K.} and Staples, {Hilary M.} and Kendra Alfson and Ricardo Carrion and Krebs, {Shelly J.} and Dominic Paquin-Proulx and Nicos Karasavva and Polonis, {Victoria R.} and Jagodzinski, {Linda L.} and Amare, {Mihret F.} and Sandhya Vasan and Scott, {Paul T.} and Yaoxing Huang and Ho, {David D.} and {de Val}, Natalia and Diamond, {Michael S.} and Lewis, {Mark G.} and Mangala Rao and Matyas, {Gary R.} and Gromowski, {Gregory D.} and Peel, {Sheila A.} and Michael, {Nelson L.} and Bolton, {Diane L.} and Kayvon Modjarrad",
note = "Funding Information: endoplasmic reticulum retention signal in the cytoplasmic tail to improve spike protein incorporation into pseudovirions (PSVs) and thereby enhance infectivity. SARS-CoV-2 PSVs were produced by cotransfection of human embryonic kidney (HEK) 293T/17 cells with a SARS-CoV-2 spike protein–expressing plasmid (pcDNA3.4), derived from the Wuhan-Hu-1 genome sequence (GenBank accession number MN908947.3) and HIV-1 (pNL4-3.Luc.R-E-, NIH HIV Reagent Program, catalog no. 3418). Infectivity and neutralization titers were determined using ACE2-expressing HEK293 target cells (Integral Molecular) in a semiautomated assay format using robotic liquid handling (Biomek NXp, Beckman Coulter). Virions pseudotyped with the vesicular stomatitis virus G protein were used as a nonspecific control. Serum samples were diluted 1:40 in growth medium [10% fetal bovine serum (FBS), 2.5% Hepes, 0.5% gentamicin, and 0.1% puromycin in Dulbecco{\textquoteright}s modified Eagle{\textquoteright}s medium]; then, 25 l per well was added, in triplicate, to a white 96-well plate. An equal volume of diluted SARS-CoV-2 PSV was added to each well, and plates were incubated for 1 hour at 37°C. Target cells were added to each well (40,000 cells per well), and plates were incubated for an additional 48 hours. Relative light units were measured with the EnVision Multimode plate reader (PerkinElmer) using the Bright-Glo Luciferase Assay System (Promega). Neutralization dose– response curves were fitted by nonlinear regression using the LabKey Server, as previously described (55). Final titers are reported as the reciprocal of the dilution of serum necessary to achieve 50% (ID50) and 90% neutralization (ID90). Assay equivalency was established by participation in the SARS-CoV-2 Neutralizing Assay Concordance Survey run by the Virology Quality Assurance Program and External Quality Assurance Program Oversite Laboratory at the Duke Human Vaccine Institute, sponsored through programs supported by the National Institute of Allergy and Infectious Diseases, Division of AIDS. Funding Information: We thank J. Lay, E. Zografos, J. Lynch, L. Mendez-Rivera, N. Jackson, B. Slike, U. Tran, S. Peters, J. Bolton, T. Robinson, E. Duncan, H. Siegfried, R.J. O'Connell, Z. Beck, and C. Alving for technical support, assistance, and advice. We acknowledge support from the U.S. Department of Defense, Defense Health Agency (Restoral FY20 to K.M.). This work was partially executed through a cooperative agreement between the U.S. Department of Defense and the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. (W81XWH-18-2-0040). The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army or the Department of Defense. Publisher Copyright: {\textcopyright} 2022 The Authors.",
year = "2022",
month = feb,
day = "16",
doi = "10.1126/scitranslmed.abi5735",
language = "English",
volume = "14",
journal = "Science Translational Medicine",
issn = "1946-6234",
number = "632",
}