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| 1 | Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates显示文摘Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COVID-19)pandemic.Plant-derived virus-like particle(VLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza.Here,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein(CoVLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)1018.Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP.Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T cells.Animals were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of SARS-CoV-2.Lower viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03.No clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated animals.The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials. | Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert V.Blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François Villinger Nathalie Landry Bali Pulendran Brian J.Ward | 2022 | Cellular & Molecular Immunology2022，19，2： | 2 |
| 2 | Perinatal hypoxia/ischemia damages and depletes progenitors from the mouse subventricular zone显示文摘 | Christine YB Robert TR Sheri B | 2004 | Dev Neurosci2004，26，： | 1 |
| 3 | Radiofrequency ablation of idiopathic left ventricular tachycardia at the site of earliest activation as determined by noncontact mapping显示文摘 | Roberts PR Allen SA | 2000 | J Cardiovasc Electrophysiol2000，11，10： | 1 |
| 4 | Ligand- independent effects of estrogen receptor beta on mouse gonadotropin-releasing hormone promoteractivity显示文摘 | Pak TR Chung WC Roberts JL | 2006 | Endocrinology2006，147，： | 1 |
| 5 | Stress analysis of bone modeling response to rat molar orthodontics显示文摘 | Paydar NH Akay HU Roberts WE | 1995 | J Biomech1995，28，1： | 1 |
| 6 | Complications of neonatal extracorporealmembraneoxyenation 显示文摘 | Zwischenberger JB Nguyen Tr Robert J | 1994 | JTberacSurg1994，107，3： | 1 |
| 7 | Electrophysiological mapping and ablation of intra-atrial reentry tachycardia after Fontan surgery with the use of a noncontact mapping system显示文摘 | Betts TR Roberts PR Allen SA | 2000 | Circulation2000，102，： | 1 |
| 8 | Chemmical studies on Mexican plants used in traditional medicineⅡ:cucurbitacins from hintonia latiflora显示文摘 | Maria TR Rachel M Robert B | | 0，，02： | 1 |
| 9 | Coffman, Heterogeneity of cytokine secretion pattems and functions of helper T cells显示文摘 | Mosmann TR Robert L | 1989 | Advances in Immunology1989，，46： | 1 |
| 10 | Widespread aneuploidy revealed by DNA microarray expression profiling显示文摘 | Hughes TR Roberts C J Dai H | 2000 | Nat Genet2000，25，： | 1 |
| 11 | Causes of pure aortic regurgi-tation in patients having isolated aortic valvereplacement at a singleUS tertiary hospital(1993 to 2005)显示文摘 | Roberts WC Ko JM Moore TR | 2006 | Circulation2006，114，5： | 1 |
| 12 | Determination of allicin, S-allylcysteine and volatile metabolites of garlic in breath, plasma or simulated gastric fluids 显示文摘 | Robert TR Richard DH Elaine KF | 2001 | Nutrition2001，131，： | 1 |
| 13 | The determination of metabolites of garlic preparations in breath and human plasma 显示文摘 | Robert TR Richard DH Elaine KF | 2000 | Biofactors2000，13，： | 1 |
| 14 | Impro- ving physical functional and quality of life in ohter adults with multiple sclerosis via a DVD-delivered exercise in- tervention: a study protocol 显示文摘 | W6jcicki TR Roberts SA Learmonth YC | 2014 | Bmj Open2014，4，12： | 1 |
| 15 | Feasibility of a left atrial electrical disconnection procedure for atrial fibrillation using transcatheter radiofrequency ablation显示文摘 | Betts TR Roberts PR Morgan JM | 2001 | J Cardiovasc Electrophysiol2001，12，11： | 1 |
| 16 | Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery显示文摘 | Pertmer TM Roberts TR Haynes JR | 1996 | J Virol1996，70，9： | 1 |
| 17 | Immediate and delayed direct pulp capping with the use of a new visible light-cured calcium hydroxide preparation显示文摘 | Pitt Ford TR Roberts GJ | 1991 | Oral Surg Oral Med Oral Pathol1991，71，3： | 1 |
| 18 | Priming with secreted glycoprotein G of respiratory syncytial virus (RSV) augments interleukin - 5 production and tissue eosinophilia after RSV challenge显示文摘 | Johnson TR Johnson JE Roberts SR | 1998 | J Virol1998，72，4： | 1 |
| 19 | Priming with secreted glycoprotein G of respiratory syncytial virus(RSV)augments interleukin-5 production and tissue eosinophilia after RSV challenge显示文摘 | Johnson TR Johnson JE Robert SR | 1998 | J Virol1998，72，4： | 1 |
| 20 | The functional consequences of airway remodeling in asthma显示文摘 | Pare PD Roberts CR Bai TR | 1997 | Monaldi Arch Chest Dis1997，52，： | 1 |
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