@article{343e2be14afd4154a2f48d55d122ea4a,
title = "A SARS-CoV-2 Spike Ferritin Nanoparticle Vaccine Is Protective and Promotes a Strong Immunological Response in the Cynomolgus Macaque Coronavirus Disease 2019 (COVID-19) Model",
abstract = "The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development and mobilization against SARS-CoV-2 (the etio-logic agent of COVID-19) has been rapid. However, novel strategies are still necessary to slow the pandemic, and this includes new approaches to vaccine development and/or delivery that will improve vaccination compliance and demonstrate efficacy against emerging variants. Here, we report on the immunogenicity and efficacy of a SARS-CoV-2 vaccine comprising stabilized, pre-fusion spike protein trimers displayed on a ferritin nanoparticle (SpFN) adjuvanted with either conven-tional aluminum hydroxide or the Army Liposomal Formulation QS-21 (ALFQ) in a cynomolgus macaque COVID-19 model. Vaccination resulted in robust cell-mediated and humoral responses and a significant reduction in lung lesions following SARS-CoV-2 infection. The strength of the immune response suggests that dose sparing through reduced or single dosing in primates may be possible with this vaccine. Overall, the data support further evaluation of SpFN as a SARS-CoV-2 protein-based vaccine candidate with attention to fractional dosing and schedule optimization.",
keywords = "Army Liposomal Formulation QS-21, COVID-19, SARS-CoV-2, SpFN, aluminum hy-droxide, ferritin nanoparticle, primate, vaccine",
author = "Johnston, {Sara C.} and Ricks, {Keersten M.} and Ines Lakhal-Naouar and Alexandra Jay and Caroline Subra and Raymond, {Jo Lynne} and King, {Hannah A.D.} and Franco Rossi and Clements, {Tamara L.} and David Fetterer and Samantha Tostenson and Cincotta, {Camila Macedo} and Hack, {Holly R.} and Caitlin Kuklis and Sandrine Soman and Jocelyn King and Peachman, {Kristina K.} and Dohoon Kim and Chen, {Wei Hung} and Sankhala, {Rajeshwer S.} and Martinez, {Elizabeth J.} and Agnes Hajduczki and Chang, {William C.} and Misook Choe and Thomas, {Paul V.} and Peterson, {Caroline E.} and Alexander Anderson and Isabella Swafford and Currier, {Jeffrey R.} and Dominic Paquin-Proulx and Jagodzinski, {Linda L.} and Matyas, {Gary R.} and Mangala Rao and Gromowski, {Gregory D.} and Peel, {Sheila A.} and Lauren White and Smith, {Jeffrey M.} and Hooper, {Jay W.} and Michael, {Nelson L.} and Kayvon Modjarrad and Joyce, {M. Gordon} and Aysegul Nalca and Bolton, {Diane L.} and Pitt, {Margaret L.M.}",
note = "Funding Information: Pseudovirion (PSV) assays against severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) and SARS-CoV-2 were performed as follows. The S expression plasmid sequence for SARS-CoV-2 was codon-optimized and modified to remove an 18-amino-acid endoplasmic reticulum retention signal in the cytoplasmic tail to improve S incorporation into PSV and thereby enhance infectivity. SARS-CoV-2 PSV were produced by co-transfection of HEK293T/17 cells with a SARS-CoV-2 S plasmid (pcDNA3.4), derived from the Wuhan-Hu-1 genome sequence (GenBank accession number: MN908947.3) and an HIV-1 (pNL4-3.Luc.R-E-, NIH HIV Reagent Program, Catalog number 3418). S expression plasmids for SARS-CoV-2 VoC were similarly codon-optimized and modified and included the following mutations: B.1.1.7 (69–70del, Y144del, N501Y, A570D, D614G, P681H, T718I, S982A, D1118H), B.1.351 (L18F, D80A, D215G, 241–243del, K417N, E484K, N501Y, D614G, A701V, E1195Q). Infectivity and neutralization titers were determined using ACE2-expressing HEK293 target cells (Integral Molecular, Philadelphia, PA, USA) in a semi-automated assay format using robotic liquid handling (Biomek NXp Beckman Coulter, Brea, CA, USA). Virions pseudotyped with the vesicular stomatitis virus (VSV) G protein were used as a non-specific control. Test sera were diluted 1:40 in growth medium and serially diluted; then, 25 µL/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 h at 37 °C. Target cells were added to each well (40,000 cells/well) and plates were incubated for an additional 48 h. Relative light units (RLU) were measured with the EnVision Multimode Plate Reader (Perkin Elmer, Waltham, MA, USA) using the Bright-Glo Luciferase Assay System (Promega, Madison, WI, USA). Neutralization dose–response curves were fitted by nonlinear regression using the LabKey Server, as previously described [25]. Final titers are reported as the reciprocal of the dilution of serum necessary to achieve 50% (ID50, 50% inhibitory dose) and 90% neutralization (ID90, 90% inhibitory dose). Assay equivalency was established by participation in the SARS-CoV-2 Neutralizing Assay Concordance Survey (SNACS) run by the Virology Quality Assurance Program and External Quality Assurance Program Oversite Laboratory (EQAPOL) at the Duke Human Vaccine Institute, sponsored through programs supported by the National Institute of Allergy and Infectious Diseases, Division of AIDS. Funding Information: Funding: Funding for this effort was provided by the Military Infectious Diseases Research Program under project number 341155776. Additionally, this work was supported by a cooperative agreement (W81XWH-18-2-0040) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. and the U.S. Department of Defense (DOD), and was supported in part by the US Army Medical Research and Development Command under contract number W81-XWH-18-C-0337. Funding for this effort was provided by the Military Infectious Diseases Research Program under project number 150155790. Publisher Copyright: {\textcopyright} 2022, MDPI. All rights reserved.",
year = "2022",
month = may,
doi = "10.3390/vaccines10050717",
language = "English",
volume = "10",
journal = "Vaccines",
issn = "2076-393X",
number = "5",
}