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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 | A DNA vaccine encoding the 42 kDa C-terminus of merozoite surface protein 1 of Plasrnodiurn falciparurn induces antibody, interferon and cytotoxic T cell responses in rhesus monkeys: immuno-stimulatory effects of granulocyte macrophage-colony stimulating factor 显示文摘 | Kumar S Villinger F Oakley M etal | 2002 | Immunology Letters2002，81，1： | 1 |
| 3 | Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine显示文摘 | Amara RR Villinger F Altman JD | | 0，，： | 1 |
| 4 | Coimmunization of rhesus macaques with plasmid vectors expressing IFN-g, GM-CSF, and SIV antigens enhances anti-viral humoral immunity but does not affect viremia after challenge with highly pathogenic virus显示文摘 | LENA P VILLINGER F GIAVEDONI L | 2002 | Vaccine2002，20，4： | 1 |
| 5 | Miniaturized data loggers for deep sea sediment temperature gradient measurements显示文摘 | Pfender M Villinger H | 2002 | Marine Geology2002，186，： | 1 |
| 6 | Role of IL-12 in HIV infection and vaccine 显示文摘 | Villinger F Ansari AA | 2010 | Eur Cytokine Netw2010，21，3： | 1 |
| 7 | Control of a mucosal challenge and prevention of clinical AIDS in rhesus monkeys by a multiprotein DNA/MVA vaccine显示文摘 | Villinger F Altman J D | 2001 | Science2001，292，： | 1 |
| 8 | Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine 显示文摘 | Amara R R Villinger F Altman J D | 2002 | Vaccine2002，20，15： | 1 |
| 9 | Post - acquisition managerial learning in central east Europe 显示文摘 | Villinger R | 1996 | Organization Studies1996，17，2： | 1 |
| 10 | Stimulation of both humoral and cellular immune response to HIV- 1 gp120 by interleukin- 12 in Rhesus macaques显示文摘 | Villinger F Ansari AA | 2002 | Vaccine2002，20，： | 1 |
| 11 | Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine显示文摘 | Amara R R Villinger F Altman J D | 2001 | Science2001，292，5514： | 1 |
| 12 | 6P challenge in DNA/MVA- vaecinated macaques显示文摘 | AMARA R R IBEGBU C VILLINGER F et ahStudies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89 | 2005 | Virology2005，343，2： | 1 |
| 13 | Dysregulation of the Polo-Like Kinase Pathway in CD4+T Cells Is Characteristic of Pathogenic Simian Immunodeficiency Virus Infection显示文摘 | Bostik P Dodd GL Villinger F | 2004 | J Virol2004，78，3： | 1 |
| 14 | Thermal conductivity measurements of rock fragments using a pulsed needle probe 显示文摘 | T J Lewis H Villinger and E E Davis | 1993 | CAN J EARTH SCI1993，30，： | 1 |
| 15 | Markedly elevated levels of interferon (IFN)-gamma, IFN-alpha, interleukin (IL)-2, IL- l0, and tumor necrosis factor-alpha associated with fatal Ebola vi- rus infection显示文摘 | Villinger F Rollin PE Brar SS | 1999 | J Infect Dis1999，179，1： | 1 |
| 16 | Simian immunodeficiency virus (SIV) infection influences the level and function of regulatory T cells in SIV-infected rhesus macaques but not SIV-infected sooty mangabeys显示文摘 | Pereira LE Villinger F Onlamoon N | 2007 | J Virol2007，81，9： | 1 |
| 17 | A new reduction algorithm for marine heat flow measurements显示文摘 | Villinger H Davis E E | 1987 | J Geophys Res1987，92，12： | 1 |
| 18 | Control of a mucosalchallenge and prevention of AIDS by a multiprotein DNA/MVA vaccine显示文摘 | Villinger F Altman JD | 2001 | Science2001，292，： | 1 |
| 19 | Miniaturized data loggers for deep sea sediment temperature gradient measurements 显示文摘 | Marion Pfender Heinrich Villinger | 2002 | Marine Geology2002，186，： | 1 |
| 20 | Miniaturized Data Loggers for Deep Sea Sediment Temperature Gradient Measurements显示文摘 | Pfender M Villinger H | 2002 | Mar Geol2002，186，： | 1 |
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