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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 | Beta2 -integrin -induced P38 MAPK activation is a key mediator in the CD14/TLR4/MD2 -depend- ent uptake of lipopolysaccharide by hepatocytes 显示文摘 | SCOTT M J BILLIAR TR | 2008 | J Biol Chem2008，283，29： | 1 |
| 3 | The chemical morphology of aggravited changes in human intervertebral discs glycosaminoglycans from cervical thoracic and lumbar nucleus palposus and anulus fibrosus显示文摘 | Bosworth TR Cribb AM | 1994 | JAnat1994，184，： | 1 |
| 4 | Anti-arrhythmic an electrophysiological effects of the endothelin receptor antagonists,BQ123 and PD161721显示文摘 | Crockett TR Scott GA McGowan NW | 2001 | Eur J Pharmacol2001，432，1： | 1 |
| 5 | Cytokeratin 18 in plasma of patients with gastrointestinal adenocarcinoma as a biomarker of tumour response显示文摘 | Scott LC Evans TR Cassidy J | 2009 | Br J Cancer2009，101，3： | 1 |
| 6 | laparoscopic cholecystectomy and common blie duct stones显示文摘 | Graham SM Flowers JL Scott TR | 1993 | Ann sure1993，218，： | 1 |
| 7 | Taste as a factor in the management of nutrition 显示文摘 | Scott TR Verhagen JV | 2000 | Ingestive Behavior Obesity2000，16，： | 1 |
| 8 | Detection of fatigue in the isometric electrical activation of paralyzed hand muscles of persons with tetraplegia显示文摘 | Heasman JM Scott TR Vare McCreey DB VA | 2000 | IEEE Trans Rehabil Eng2000，8，3： | 1 |
| 9 | Taste as a factor in the management of nutrition 显示文摘 | Scott TR Verhagen JV | 2000 | Nutrition2000，16，10： | 1 |
| 10 | Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14lTLR4lMD2-dependent uptake of li- popolysaccharide by hepatocytes 显示文摘 | Scott M J Billiar TR | 2008 | J Biol Chem2008，283，29： | 1 |
| 11 | Unilateral Superior Rectus Recession for the Treatment of Dissociated Vertical Deviation显示文摘 | Schwartz TR Scott WL | 1991 | Journal of Pediatric Ophthalmology and Strabismus1991，28，4： | 1 |
| 12 | Hepatocytes en- hance effects of lipopolysaccharide on liver nonparenchymal cells through close cell interactions显示文摘 | Scott M J Liu S Su GL Vodovotz Y Billiar TR | 2005 | Shock2005，23，5： | 1 |
| 13 | Treatment of medically and surgically refractory angina pectoris with high thoracic epidural analgesia: initial clinical experience显示文摘 | Michael JM Scott TR | 1997 | Am Heart J1997，133，11： | 1 |
| 14 | Anti-arrhythmic an electrophysiological effects of the endothelin receptor antagonists,BQ123 and PD161721 显示文摘 | Crockett TR Scott GA McGowan NW | 2001 | Eur J Pharmacol2001，432，1： | 1 |
| 15 | Blood flow and venous ulcers显示文摘 | Cheatle TR Scott HI Scurf JH | 1991 | Br J D erm atol1991，125，： | 1 |
| 16 | An- ti-arrhythmic an electrophysiological effects of the endothelin receptor antagonists, BQ-123 and PD161721显示文摘 | Crockett TR Scott GA McGowan NW | 2001 | Eur J Pharmacol2001，432，1： | 1 |
| 17 | Treatment of medically- and surgically refractory angina pectoriswith high thoracic epidural an- algesia:initial clinical experience显示文摘 | Grambling-Babb P Michael JM Scott TR | 1997 | Am Heart J1997，133，6： | 1 |
| 18 | Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2- dependent uptake of lipopolysaccharide by hepatocytes显示文摘 | Scott MJ Billiar TR | 2008 | J Biol Chem2008，283，29： | 1 |
| 19 | Treatment of medically and surgically refractory angina pectoris with high thoracic epidural analgesia: initial clinical experience显示文摘 | Grambling-Babb P Michael JM Scott TR | 1997 | Am Heart J1997，133，： | 1 |
| 20 | The effects of low intensity radiofrequency electromagnetic fields on electrical activity in rat hippocampal slices显示文摘 | Tattersall JE Scott TR Wood SJ | 2001 | Brain Res2001，904，： | 1 |
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