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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 | 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 |
| 3 | 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 |
| 4 | Post - acquisition managerial learning in central east Europe 显示文摘 | Villinger R | 1996 | Organization Studies1996，17，2： | 1 |
| 5 | 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 |
| 6 | 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 |
| 7 | Rates of fluid expulsion across the northern Cascadia accretionary prism: constraints from new heat flow and multichannel seismic reflection data 显示文摘 | Davis E E Hyndman R D Villinger H | 1990 | J Geophys Res1990，95，： | 1 |
| 8 | Different patterns of immune responses but similar control of a mucosal immunodeficiency virus challenge by MVA and DNA-MVA vaccines显示文摘 | Villinger F Staprans S I | 2002 | J Virol2002，76，： | 1 |
| 9 | Evidence for antibody-mediated enhancement of simian immunodeficiency virus(SIV)Gag antigen processing and cross presentation in SIV-infected rhesus macaques显示文摘 | Villinger F Mayne A E Bostik P Mori K Jensen P E Ahmed R Ansari A A | | 0，，01： | 1 |
| 10 | Rates of fluid expulsion across the northern Cascadia accretionary prism:Constraints from new heat flow and multichannel seismic reflection data显示文摘 | Davis E E Hyndman R D Villinger H | 1990 | Journal of Geophysical Research1990，95，： | 1 |
| 11 | Post-acquisition managerial learning in central east Europe 显示文摘 | | 1996 | Organization Studies1996，17，： | 1 |
| 12 | 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 |
| 13 | Rates of fluid expulsion across the northern Cascadia accretionary prism: constraints from new heat flow and multichannel seismic reflection data 显示文摘 | Davis E E Hyndman R D Villinger H | 1990 | Jour- nal of Geophysical Research1990，95，6： | 1 |
| 14 | Control of a mucosal challenge and prevention of AIDS by a muhiprotein DNA/MVA vaccine 显示文摘 | Amara R R Villinger F | 2001 | Science2001，292，： | 1 |
| 15 | A robust rapid-reponse probe for measuring bottom-hole temperatures in deep-ocean boreholes显示文摘 | Davis E E Villinger H McDonald R D | 1997 | Mar Geophys Res1997，19，： | 1 |
| 16 | A Robust Rapid-response Probe for Measuring Bottom-hole Temperatures in Deep-ocean Boreholes显示文摘 | Davis E E Villinger H MacDonald R D | 1997 | Marine Geophysical Researches1997，19，3： | 1 |
| 17 | IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T cells in rhesus macaques 显示文摘 | Villinger F Miller R Mori K | 2008 | Vaccine2008，26，40： | 1 |
| 18 | Rates of fluid expulsion across the northern Cascadia accretionary prism: constraints from new heat flow and muhichannel seismic reflection data显示文摘 | Davis E E Hyndman R D Villinger H | 1990 | Journal of Geophysics Research1990，95，： | 1 |
| 19 | Post-acquisition Managerial Learning in Central East Europe显示文摘 | Villinger R | 1996 | Organization Studies1996，，17： | 1 |
| 20 | The role of gamma delta T cells in generating antiviral factors and beta-chemokines in protection against mucosal simian immunodeficiency virus infection显示文摘 | Lehner T Mitchell E Bergmeier L Singh M Spallek R Cranage M Hall G Dennis M Villinger F Wang Y | 2000 | Eur J Immunol2000，30，8： | 1 |
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