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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 | The pathogenesis of vasodilatory shock 显示文摘 | Landry D W Oliver J A | 2001 | N Engl J Med2001，345，45： | 1 |
| 3 | Vasopressin pressorhypersensitivity in vasodilatory septic shock显示文摘 | Landry D W Levin D R Gallant E M | 1997 | Crit Care Med1997，25，8： | 1 |
| 4 | A placebo controlledmulticentre evaluation of an anaesthetic gel(Oraqix) for periodontal therapy显示文摘 | Adonaldson D Gelskey SC Landry RG | 2003 | J Clin Periodontal2003，30，： | 1 |
| 5 | Science Review: Vasopressin and the cardiovascular system part 2 -clinical physiology 显示文摘 | Holmes C L Landry D W Granton J T | 2004 | Crit Care2004，8，1： | 1 |
| 6 | The pathogenesis of vasodilamry shock显示文摘 | LANDRY D W OLIVER J A | 2001 | N Engl J Med2001，345，： | 1 |
| 7 | Spheroidal aggregate culture of rat liver cells:histotypic reorganization,biomatrix deposition,and maintenance of functional activities显示文摘 | Landry J Bernier D Ouel et C | | 0，，03： | 1 |
| 8 | Bedside teaching显示文摘 | Kroenke K Omori D M Landry F J | 1997 | Southern Medical Journal1997，，90： | 1 |
| 9 | Foodbome outbreaks in Canada linked to produce : 2001 through 2009 显示文摘 | Kozak GK MacDonald D Landry L | 2013 | J Food Prot2013，76，1： | 1 |
| 10 | Identification of functional microRNAs released through asymmetrical processing of HIV-I TAR element显示文摘 | Ouellet D L Plante I Landry P | 2008 | Nucleic Acids Res2008，36，7： | 1 |
| 11 | Reaction pathways and energy barriers for alkaline hydrolysis of carboxylic acid esters in water studied by a hybrid supermolecule-polarizable continuum approach显示文摘 | Landry D W Ornstein R L | 2000 | J Am Chem Soc2000，122，： | 1 |
| 12 | Measurement of accelerator bremsstrahlung safeclean with a high efficiency Ge detector显示文摘 | LANDRY D J ANDERSON D W | 1991 | Med Phys1991，18，： | 1 |
| 13 | Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition and maintenance of functional activities 显示文摘 | Landry J Bemier D | 1985 | J Cell Biol1985，101，： | 1 |
| 14 | Fundamental reaction mechanism for cocaine hydrolysis in human butyrylcholinesterase显示文摘 | Zhan Changguo Zheng Fang Landry D W | 2003 | J Am Chem Soc2003，125，： | 1 |
| 15 | Tetrahedron显示文摘 | Zhao K Landry D W | 1993 | 49:3631993，49，： | 1 |
| 16 | In-situ Polymerizaion of Tetraethoxysilane in Polymers: Chemical Nature of the interacions显示文摘 | LANDRY D J T COLTRAIN B K WESSON J A | 1992 | Polymer1992，33，7： | 1 |
| 17 | Foodborne outbreaks in Canada linked to produce: 2001 through 2009显示文摘 | Kozak G K MacDonald D Landry L | 2013 | JFoodProt2013，76，1： | 1 |
| 18 | Aptamerbased folding fluorescent sensor for cocaine显示文摘 | STOJANOVIC M N DE PRADA P LANDRY D W | 2001 | Journal of the American Chemical Society2001，123，21： | 1 |
| 19 | Supply chain proeess integration: A theoretieal framework 显示文摘 | Chen H Daugherty P J Landry T D | 2009 | Journal of Business Logistics2009，30，2： | 1 |
| 20 | Occurrence and severity of bronchopulmonary dysplasia and respiratory dis- tress syndrome after a preterm birth显示文摘 | Landry JS Menzies D | 2011 | Paediatr Child Health2011，16，7： | 1 |
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