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1. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial

Author

Ziviani, Luigi, Malescio, Feliciana, Turrini, Irene, Lawlor, Rita, Romano, Annamaria, Nunziata, Mariagrazia, Armato, Salvatore, Mazzeo, Nicole, Carleo, Maria Aurora, Dell’Isola, Chiara, Pisapia, Raffaella, Pontarelli, Agostina, Olivani, Andrea, Grasselli, Sara, Laccabue, Diletta, Leoni, Maria Cristina, Paolillo, Franco, Mancini, Annalisa, Ruaro, Barbara, Confalonieri, Marco, Salton, Francesco, Mancarella, Giulia, Marocco, Raffaella, De Masi, Margherita, Belvisi, Valeria, Lamonica, Silvia, Cingolani, Antonella, Seguiti, Cristina, Brambilla, Paola, Ferraresi, Alice, Lupi, Matteo, Ludovisi, Serena, Renisi, Giulia, Massafra, Roberta, Pellicciotta, Martina, Armiento, Luciana, Vimercati, Stefania, Piacenza, Mariagrazia, Bonfanti, Paolo, Columpsi, Paola, Cazzaniga, Marina Elena, Rovelli, Cristina, Ceresini, Mariaelena, Previtali, Letizia, Trentini, Laura, Alcantarini, Chiara, Rugge, Walter, Biffi, Stefano, Poletti, Federica, Rostagno, Roberto, Moglia, Roberta, De Negri, Ferdinando, Fini, Elisabetta, Cangialosi, Alice, Bruno, Serena Rita, Rizzo, Marianna, Niglio, Mariangela, Stritto, Anna Dello, Matano, Alfredo, Petruzziello, Arnolfo, Valsecchi, Pietro, Pieri, Teresa, Altamura, Mauro, Calamo, Angela, Giannelli, Anna, Menolascina, Stefania, Di Bari, Silvia, Mauro, Vera, Aronica, Raissa, Segala, Daniela, Cultrera, Rosario, Sighinolfi, Laura, Abbott, Michelle, Gizzi, Andrea, Marascia, Federica Guida, Valenti, Giacomo, Feasi, Marcello, Bobbio, Nicoletta, Del Puente, Filippo, Nicosia, Alfredo, Frascà, Martina, Mazzoleni, Miriam, Garofalo, Nadia, Ammendola, Virginia, Grazioli, Fabiana, Napolitano, Federico, Vitelli, Alessandra, Marcellini, Valentina, Capone, Stefania, Fusco, Francesco M., Milleri, Stefano, Borrè, Silvio, Carbonara, Sergio, Lo Caputo, Sergio, Leone, Sebastiano, Gori, Giovanni, Maggi, Paolo, Cascio, Antonio, Lichtner, Miriam, Cauda, Roberto, Dal Zoppo, Sarah, Cossu, Maria V., Gori, Andrea, Roda, Silvia, Confalonieri, Paola, Bonora, Stefano, Missale, Gabriele, Codeluppi, Mauro, Mezzaroma, Ivano, Capici, Serena, Pontali, Emanuele, Libanore, Marco, Diani, Augusta, Lanini, Simone, Battella, Simone, Contino, Alessandra M., Piano Mortari, Eva, Genova, Francesco, Parente, Gessica, Dragonetti, Rosella, Colloca, Stefano, Visani, Luigi, Iannacone, Claudio, Carsetti, Rita, Folgori, Antonella, and Camerini, Roberto

Published
2023
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2. Efficacy, pharmacokinetics, and safety in the mouse and primate retina of dual AAV vectors for Usher syndrome type 1B

Author

Ferla, Rita, Dell’Aquila, Fabio, Doria, Monica, Ferraiuolo, Maria, Noto, Alessia, Grazioli, Fabiana, Ammendola, Virginia, Testa, Francesco, Melillo, Paolo, Iodice, Carolina, Risca, Giulia, Tedesco, Novella, le Brun, Pierre Romain, Surace, Enrico Maria, Simonelli, Francesca, Galimberti, Stefania, Valsecchi, Maria Grazia, Marteau, Jean-Brice, Veron, Philippe, Colloca, Stefano, and Auricchio, Alberto

Published
2023
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3. GRAd-COV2, a gorilla adenovirus-based candidate vaccine against COVID-19, is safe and immunogenic in younger and older adults

Author

Lanini, Simone, primary, Capone, Stefania, additional, Antinori, Andrea, additional, Milleri, Stefano, additional, Nicastri, Emanuele, additional, Camerini, Roberto, additional, Agrati, Chiara, additional, Castilletti, Concetta, additional, Mori, Federica, additional, Sacchi, Alessandra, additional, Matusali, Giulia, additional, Gagliardini, Roberta, additional, Ammendola, Virginia, additional, Cimini, Eleonora, additional, Grazioli, Fabiana, additional, Scorzolini, Laura, additional, Napolitano, Federico, additional, Plazzi, Maria M., additional, Soriani, Marco, additional, De Luca, Aldo, additional, Battella, Simone, additional, Sommella, Andrea, additional, Contino, Alessandra M., additional, Barra, Federica, additional, Gentile, Michela, additional, Raggioli, Angelo, additional, Shi, Yufang, additional, Girardi, Enrico, additional, Maeurer, Markus, additional, Capobianchi, Maria R., additional, Vaia, Francesco, additional, Piacentini, Mauro, additional, Kroemer, Guido, additional, Vitelli, Alessandra, additional, Colloca, Stefano, additional, Folgori, Antonella, additional, and Ippolito, Giuseppe, additional

Published
2022
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4. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Author

Stanley, Daphne A., Honko, Anna N., Asiedu, Clement, Trefry, John C., Lau-Kilby, Annie W., Johnson, Joshua C., Hensley, Lisa, Ammendola, Virginia, Abbate, Adele, Grazioli, Fabiana, Foulds, Kathryn E., Cheng, Cheng, Wang, Lingshu, Donaldson, Mitzi M., Colloca, Stefano, Folgori, Antonella, Roederer, Mario, Nabel, Gary J., Mascola, John, Nicosia, Alfredo, Cortese, Riccardo, Koup, Richard A., and Sullivan, Nancy J.

Subjects
Viral vaccines -- Research -- Analysis -- Physiological aspects, Ebola virus -- Research -- Analysis, Biological sciences, Health
Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge., Human-derived rAd vectors have undergone extensive development in preclinical and human trials as vaccines for multiple pathogens (1-6). For ebolavirus, rAd vaccines that confer protection against acute EBOV challenge generate [...]

Published
2014
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5. Chronic hepatitis C viral infection subverts vaccine-induced T-cell immunity in humans

Author

Kelly, Christabel, Swadling, Leo, Capone, Stefania, Brown, Anthony, Richardson, Rachel, Halliday, John, von Delft, Annette, Oo, Ye, Mutimer, David, Kurioka, Ayako, Hartnell, Felicity, Collier, Jane, Ammendola, Virginia, Sorbo, Mariarosaria Del, Grazioli, Fabiana, Esposito, Maria Luisa, Marco, Stefania Di, Siani, Loredana, Traboni, Cinzia, Hill, Adrian V.S., Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, Folgori, Antonella, Klenerman, Paul, and Barnes, Eleanor

Published
2016
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6. GRAd-COV2, a gorilla adenovirus based candidate vaccine against COVID-19, is safe and immunogenic in young and older adults

Author

Lanini, Simone, primary, Capone, Stefania, additional, Antinori, Andrea, additional, Milleri, Stefano, additional, Nicastri, Emanuele, additional, Camerini, Roberto, additional, Agrati, Chiara, additional, Castilletti, Concetta, additional, Mori, Federica, additional, Sacchi, Alessandra, additional, Matusali, Giulia, additional, Gagliardini, Roberta, additional, Ammendola, Virginia, additional, Cimini, Eleonora, additional, Grazioli, Fabiana, additional, Scorzolini, Laura, additional, Napolitano, Federico, additional, Piazzi, Maria Maddalena, additional, Soriani, Marco, additional, De Luca, Aldo, additional, Battella, Simone, additional, Sommella, Andrea, additional, Contino, Alessandra M., additional, Barra, Federica, additional, Gentile, Michela, additional, Raggioli, Angelo, additional, Shi, Yufang, additional, Girardi, Enrico, additional, Maeurer, Markus, additional, Capobianchi, Maria R., additional, Vaia, Francesco, additional, Piacentini, Mauro, additional, Kroemer, Guido, additional, Vitelli, Alessandra, additional, Colloca, Stefano, additional, Folgori, Antonella, additional, and Ippolito, Giuseppe, additional

Published
2021
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7. Correction: A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Author

Napolitano, Federico, primary, Merone, Rossella, additional, Abbate, Adele, additional, Ammendola, Virginia, additional, Horncastle, Emma, additional, Lanzaro, Francesca, additional, Esposito, Marialuisa, additional, Contino, Alessandra Maria, additional, Sbrocchi, Roberta, additional, Sommella, Andrea, additional, Duncan, Joshua D., additional, Hinds, Joseph, additional, Urbanowicz, Richard A., additional, Lahm, Armin, additional, Colloca, Stefano, additional, Folgori, Antonella, additional, Ball, Jonathan K., additional, Nicosia, Alfredo, additional, Wizel, Benjamin, additional, Capone, Stefania, additional, and Vitelli, Alessandra, additional

Published
2021
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8. MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans

Author

Esposito, Ilaria, Cicconi, Paola, D'Alise, Anna Morena, Brown, Anthony, Esposito, Marialuisa, Swadling, Leo, Holst, Peter Johannes, Bassi, Maria Rosaria, Stornaiuolo, Mariano, Mori, Federica, Vassilev, Ventzislav, Li, Wenqin, Donnison, Timothy, Gentile, Chiara, Turner, Bethany, von Delft, Annette, Del Sorbo, Mariarosaria, Barra, Federica, Contino, Alessandra Maria, Abbate, Adele, Novellino, Ettore, Thomsen, Allan Randrup, Christensen, Jan Pravsgaard, Lahm, Armin, Grazioli, Fabiana, Ammendola, Virginia, Siani, Loredana, Colloca, Stefano, Klenerman, Paul, Nicosia, Alfredo, Dorrell, Lucy, Folgori, Antonella, Capone, Stefania, Barnes, Eleanor, Esposito, Ilaria, Cicconi, Paola, D'Alise, Anna Morena, Brown, Anthony, Esposito, Marialuisa, Swadling, Leo, Holst, Peter Johannes, Bassi, Maria Rosaria, Stornaiuolo, Mariano, Mori, Federica, Vassilev, Ventzislav, Li, Wenqin, Donnison, Timothy, Gentile, Chiara, Turner, Bethany, von Delft, Annette, Del Sorbo, Mariarosaria, Barra, Federica, Contino, Alessandra Maria, Abbate, Adele, Novellino, Ettore, Thomsen, Allan Randrup, Christensen, Jan Pravsgaard, Lahm, Armin, Grazioli, Fabiana, Ammendola, Virginia, Siani, Loredana, Colloca, Stefano, Klenerman, Paul, Nicosia, Alfredo, Dorrell, Lucy, Folgori, Antonella, Capone, Stefania, and Barnes, Eleanor

Abstract

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+CD8+ cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections.

Published
2020

10. A next generation vaccine against human rabies based on a single dose of a chimpanzee adenovirus vector serotype C

Author

Napolitano, Federico, primary, Merone, Rossella, additional, Abbate, Adele, additional, Ammendola, Virginia, additional, Horncastle, Emma, additional, Lanzaro, Francesca, additional, Esposito, Marialuisa, additional, Contino, Alessandra Maria, additional, Sbrocchi, Roberta, additional, Sommella, Andrea, additional, Duncan, Joshua D., additional, Hinds, Jospeh, additional, Urbanowicz, Richard A., additional, Lahm, Armin, additional, Colloca, Stefano, additional, Folgori, Antonella, additional, Ball, Jonathan K., additional, Nicosia, Alfredo, additional, Wizel, Benjamin, additional, Capone, Stefania, additional, and Vitelli, Alessandra, additional

Published
2020
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12. CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient

Author

Benati, Daniela, primary, Miselli, Francesca, additional, Cocchiarella, Fabienne, additional, Patrizi, Clarissa, additional, Carretero, Marta, additional, Baldassarri, Samantha, additional, Ammendola, Virginia, additional, Has, Cristina, additional, Colloca, Stefano, additional, Del Rio, Marcela, additional, Larcher, Fernando, additional, and Recchia, Alessandra, additional

Published
2018
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13. Highly-Immunogenic Virally-Vectored T-cell Vaccines Cannot Overcome Subversion of the T-cell Response by HCV during Chronic Infection

Author

Swadling, Leo, primary, Halliday, John, additional, Kelly, Christabel, additional, Brown, Anthony, additional, Capone, Stefania, additional, Ansari, M., additional, Bonsall, David, additional, Richardson, Rachel, additional, Hartnell, Felicity, additional, Collier, Jane, additional, Ammendola, Virginia, additional, Del Sorbo, Mariarosaria, additional, Von Delft, Annette, additional, Traboni, Cinzia, additional, Hill, Adrian, additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, Klenerman, Paul, additional, Folgori, Antonella, additional, and Barnes, Eleanor, additional

Published
2016
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14. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

Author

Pierantoni, Angiolo, primary, Esposito, Maria Luisa, additional, Ammendola, Virginia, additional, Napolitano, Federico, additional, Grazioli, Fabiana, additional, Abbate, Adele, additional, del Sorbo, Mariarosaria, additional, Siani, Loredana, additional, D'Alise, Anna Morena, additional, Taglioni, Alessandra, additional, Perretta, Gemma, additional, Siccardi, Antonio, additional, Soprana, Elisa, additional, Panigada, Maddalena, additional, Thom, Michelle, additional, Scarselli, Elisa, additional, Folgori, Antonella, additional, Colloca, Stefano, additional, Taylor, Geraldine, additional, Cortese, Riccardo, additional, Nicosia, Alfredo, additional, Capone, Stefania, additional, and Vitelli, Alessandra, additional

Published
2015
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15. A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory

Author

Swadling, Leo, primary, Capone, Stefania, additional, Antrobus, Richard D., additional, Brown, Anthony, additional, Richardson, Rachel, additional, Newell, Evan W., additional, Halliday, John, additional, Kelly, Christabel, additional, Bowen, Dan, additional, Fergusson, Joannah, additional, Kurioka, Ayako, additional, Ammendola, Virginia, additional, Del Sorbo, Mariarosaria, additional, Grazioli, Fabiana, additional, Esposito, Maria Luisa, additional, Siani, Loredana, additional, Traboni, Cinzia, additional, Hill, Adrian, additional, Colloca, Stefano, additional, Davis, Mark, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, Folgori, Antonella, additional, Klenerman, Paul, additional, and Barnes, Eleanor, additional

Published
2014
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16. Combined Adenovirus Vector and Hepatitis C Virus Envelope Protein Prime-Boost Regimen Elicits T Cell and Neutralizing Antibody Immune Responses

Author

Chmielewska, Alicja M., primary, Naddeo, Mariarosaria, additional, Capone, Stefania, additional, Ammendola, Virginia, additional, Hu, Ke, additional, Meredith, Luke, additional, Verhoye, Lieven, additional, Rychlowska, Malgorzata, additional, Rappuoli, Rino, additional, Ulmer, Jeffrey B., additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, Leroux-Roels, Geert, additional, Balfe, Peter, additional, Bienkowska-Szewczyk, Krystyna, additional, Meuleman, Philip, additional, McKeating, Jane A., additional, and Folgori, Antonella, additional

Published
2014
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17. Fusion of HCV Nonstructural Antigen to MHC Class II–associated Invariant Chain Enhances T-cell Responses Induced by Vectored Vaccines in Nonhuman Primates

Author

Capone, Stefania, primary, Naddeo, Mariarosaria, additional, D'Alise, Anna Morena, additional, Abbate, Adele, additional, Grazioli, Fabiana, additional, Del Gaudio, Annunziata, additional, Del Sorbo, Mariarosaria, additional, Esposito, Maria Luisa, additional, Ammendola, Virginia, additional, Perretta, Gemma, additional, Taglioni, Alessandra, additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, and Folgori, Antonella, additional

Published
2014
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18. CRISPR/Cas9-Mediated In SituCorrection of LAMB3 Gene in Keratinocytes Derived from a Junctional Epidermolysis Bullosa Patient

Author

Benati, Daniela, Miselli, Francesca, Cocchiarella, Fabienne, Patrizi, Clarissa, Carretero, Marta, Baldassarri, Samantha, Ammendola, Virginia, Has, Cristina, Colloca, Stefano, Del Rio, Marcela, Larcher, Fernando, and Recchia, Alessandra

Abstract

Deficiency of basement membrane heterotrimeric laminin 332 component, coded by LAMA3, LAMB3, and LAMC2genes, causes junctional epidermolysis bullosa (JEB), a severe skin adhesion defect. Herein, we report the first application of CRISPR/Cas9-mediated homology direct repair (HDR) to in siturestore LAMB3 expression in JEB keratinocytes in vitroand in immunodeficient mice transplanted with genetically corrected skin equivalents. We packaged an adenovector carrying Cas9/guide RNA (gRNA) tailored to the intron 2 of LAMB3gene and an integration defective lentiviral vector bearing a promoterless quasi-complete LAMB3cDNA downstream a splice acceptor site and flanked by homology arms. Upon genuine HDR, we exploited the in vitroadhesion advantage of laminin 332 production to positively select LAMB3-expressing keratinocytes. HDR and restored laminin 332 expression were evaluated at single-cell level. Notably, monoallelic-targeted integration of LAMB3cDNA was sufficient to in vitrorecapitulate the adhesive property, the colony formation typical of normal keratinocytes, as well as their cell growth. Grafting of genetically corrected skin equivalents onto immunodeficient mice showed a completely restored dermal-epidermal junction. This study provides evidence for efficient CRISPR/Cas9-mediated in siturestoration of LAMB3 expression, paving the way for ex vivoclinical application of this strategy to laminin 332 deficiency.

Published
2018
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19. Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus

Author

Vitelli, Alessandra, primary, Quirion, Mary R., additional, Lo, Chia-Yun, additional, Misplon, Julia A., additional, Grabowska, Agnieszka K., additional, Pierantoni, Angiolo, additional, Ammendola, Virginia, additional, Price, Graeme E., additional, Soboleski, Mark R., additional, Cortese, Riccardo, additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, and Epstein, Suzanne L., additional

Published
2013
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20. Novel Adenovirus-Based Vaccines Induce Broad and Sustained T Cell Responses to HCV in Man

Author

Barnes, Eleanor, primary, Folgori, Antonella, additional, Capone, Stefania, additional, Swadling, Leo, additional, Aston, Stephen, additional, Kurioka, Ayako, additional, Meyer, Joel, additional, Huddart, Rachel, additional, Smith, Kira, additional, Townsend, Rachel, additional, Brown, Anthony, additional, Antrobus, Richard, additional, Ammendola, Virginia, additional, Naddeo, Mariarosaria, additional, O’Hara, Geraldine, additional, Willberg, Chris, additional, Harrison, Abby, additional, Grazioli, Fabiana, additional, Esposito, Maria Luisa, additional, Siani, Loredana, additional, Traboni, Cinzia, additional, Oo, Ye, additional, Adams, David, additional, Hill, Adrian, additional, Colloca, Stefano, additional, Nicosia, Alfredo, additional, Cortese, Riccardo, additional, and Klenerman, Paul, additional

Published
2012
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21. Vaccine Vectors Derived from a Large Collection of Simian Adenoviruses Induce Potent Cellular Immunity Across Multiple Species

Author

Colloca, Stefano, primary, Barnes, Eleanor, additional, Folgori, Antonella, additional, Ammendola, Virginia, additional, Capone, Stefania, additional, Cirillo, Agostino, additional, Siani, Loredana, additional, Naddeo, Mariarosaria, additional, Grazioli, Fabiana, additional, Esposito, Maria Luisa, additional, Ambrosio, Maria, additional, Sparacino, Angela, additional, Bartiromo, Marta, additional, Meola, Annalisa, additional, Smith, Kira, additional, Kurioka, Ayako, additional, O’Hara, Geraldine A., additional, Ewer, Katie J., additional, Anagnostou, Nicholas, additional, Bliss, Carly, additional, Hill, Adrian V. S., additional, Traboni, Cinzia, additional, Klenerman, Paul, additional, Cortese, Riccardo, additional, and Nicosia, Alfredo, additional

Published
2012
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22. Immune responses against a liver-stage malaria antigen induced by simian adenoviral vector AdCh63 and MVA prime–boost immunisation in non-human primates

Author

Capone, Stefania, primary, Reyes-Sandoval, Arturo, additional, Naddeo, Mariarosaria, additional, Siani, Loredana, additional, Ammendola, Virginia, additional, Rollier, Christine S., additional, Nicosia, Alfredo, additional, Colloca, Stefano, additional, Cortese, Riccardo, additional, Folgori, Antonella, additional, and Hill, Adrian V.S., additional

Published
2010
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23. Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques

Author

Rosario, Maximillian, primary, Bridgeman, Anne, additional, Quakkelaar, Esther D., additional, Quigley, Maire F., additional, Hill, Brenna J., additional, Knudsen, Maria L., additional, Ammendola, Virginia, additional, Ljungberg, Karl, additional, Borthwick, Nicola, additional, Im, Eung-Jun, additional, McMichael, Andrew J., additional, Drijfhout, Jan W., additional, Greenaway, Hui Yee, additional, Venturi, Vanessa, additional, Douek, Daniel C., additional, Colloca, Stefano, additional, Liljeström, Peter, additional, Nicosia, Alfredo, additional, Price, David A., additional, Melief, Cornelis J. M., additional, and Hanke, Tomás̆, additional

Published
2010
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24. Differential Screening of Phage-Ab Libraries by Oligonucleotide Microarray Technology

Author

Monaci, Paolo, primary, Luzzago, Alessandra, additional, Santini, Claudia, additional, De Pra, Alessandra, additional, Arcuri, Mirko, additional, Magistri, Francesca, additional, Bellini, Alessandro, additional, Ansuini, Helenia, additional, Ambrosio, Maria, additional, Ammendola, Virginia, additional, Bigotti, Maria Giulia, additional, Cirillo, Agostino, additional, Nuzzo, Maurizio, additional, Nasti, Annamaria Assunta, additional, Neuner, Philippe, additional, Orsatti, Laura, additional, Pezzanera, Monica, additional, Sbardellati, Andrea, additional, Silvestre, Giuseppe, additional, Uva, Paolo, additional, Viti, Valentina, additional, Barbato, Gaetano, additional, Colloca, Stefano, additional, Demartis, Anna, additional, De Rinaldis, Emanuele, additional, Giampaoli, Saverio, additional, Lahm, Armin, additional, Palombo, Fabio, additional, Talamo, Fabio, additional, Vitelli, Alessandra, additional, Nicosia, Alfredo, additional, and Cortese, Riccardo, additional

Published
2008
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26. GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial (COVITAR)

Author

Capone, Stefania, Fusco, Francesco M., Milleri, Stefano, Borrè, Silvio, Carbonara, Sergio, Lo Caputo, Sergio, Leone, Sebastiano, Gori, Giovanni, Maggi, Paolo, Cascio, Antonio, Lichtner, Miriam, Cauda, Roberto, Zoppo, Sarah Dal, Cossu, Maria V., Gori, Andrea, Roda, Silvia, Confalonieri, Paola, Bonora, Stefano, Missale, Gabriele, Codeluppi, Mauro, Mezzaroma, Ivano, Capici, Serena, Pontali, Emanuele, Libanore, Marco, Diani, Augusta, Lanini, Simone, Battella, Simone, Contino, Alessandra M., Mortari, Eva Piano, Genova, Francesco, Parente, Gessica, Dragonetti, Rosella, Colloca, Stefano, Visani, Luigi, Iannacone, Claudio, Carsetti, Rita, Folgori, Antonella, Camerini, Roberto, Ziviani, Luigi, Malescio, Feliciana, Turrini, Irene, Lawlor, Rita, Romano, Annamaria, Nunziata, Mariagrazia, Armato, Salvatore, Mazzeo, Nicole, Carleo, Maria Aurora, Dell’Isola, Chiara, Pisapia, Raffaella, Pontarelli, Agostina, Olivani, Andrea, Grasselli, Sara, Laccabue, Diletta, Leoni, Maria Cristina, Paolillo, Franco, Mancini, Annalisa, Ruaro, Barbara, Confalonieri, Marco, Salton, Francesco, Mancarella, Giulia, Marocco, Raffaella, De Masi, Margherita, Belvisi, Valeria, Lamonica, Silvia, Cingolani, Antonella, Seguiti, Cristina, Brambilla, Paola, Ferraresi, Alice, Lupi, Matteo, Ludovisi, Serena, Renisi, Giulia, Massafra, Roberta, Pellicciotta, Martina, Armiento, Luciana, Vimercati, Stefania, Piacenza, Mariagrazia, Bonfanti, Paolo, Columpsi, Paola, Cazzaniga, Marina Elena, Rovelli, Cristina, Ceresini, Mariaelena, Previtali, Letizia, Trentini, Laura, Alcantarini, Chiara, Rugge, Walter, Biffi, Stefano, Poletti, Federica, Rostagno, Roberto, Moglia, Roberta, De Negri, Ferdinando, Fini, Elisabetta, Cangialosi, Alice, Bruno, Serena Rita, Rizzo, Marianna, Niglio, Mariangela, Stritto, Anna Dello, Matano, Alfredo, Petruzziello, Arnolfo, Valsecchi, Pietro, Pieri, Teresa, Altamura, Mauro, Calamo, Angela, Giannelli, Anna, Menolascina, Stefania, Di Bari, Silvia, Mauro, Vera, Aronica, Raissa, Segala, Daniela, Cultrera, Rosario, Sighinolfi, Laura, Abbott, Michelle, Gizzi, Andrea, Marascia, Federica Guida, Valenti, Giacomo, Feasi, Marcello, Bobbio, Nicoletta, Del Puente, Filippo, Nicosia, Alfredo, Frascà, Martina, Mazzoleni, Miriam, Garofalo, Nadia, Ammendola, Virginia, Grazioli, Fabiana, Napolitano, Federico, Vitelli, Alessandra, and Marcellini, Valentina

Abstract

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and heterologous immunization approaches implemented worldwide for booster doses call for diversified vaccine portfolios. GRAd-COV2 is a gorilla adenovirus-based COVID-19 vaccine candidate encoding prefusion-stabilized spike. The safety and immunogenicity of GRAd-COV2 is evaluated in a dose- and regimen-finding phase 2 trial (ClinicalTrials.gov: NCT04791423) whereby 917 eligible participants are randomized to receive a single intramuscular GRAd-COV2 administration followed by placebo, or two vaccine injections, or two doses of placebo, spaced over 3 weeks. Here, we report that GRAd-COV2 is well tolerated and induces robust immune responses after a single immunization; a second administration increases binding and neutralizing antibody titers. Potent, variant of concern (VOC) cross-reactive spike-specific T cell response peaks after the first dose and is characterized by high frequencies of CD8s. T cells maintain immediate effector functions and high proliferative potential over time. Thus, GRAd vector is a valuable platform for genetic vaccine development, especially when robust CD8 response is needed.

Published
2023
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27. Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus.

Author

Vitelli, Alessandra, Quirion, Mary R., Lo, Chia-Yun, Misplon, Julia A., Grabowska, Agnieszka K., Pierantoni, Angiolo, Ammendola, Virginia, Price, Graeme E., Soboleski, Mark R., Cortese, Riccardo, Colloca, Stefano, Nicosia, Alfredo, and Epstein, Suzanne L.

Subjects
INFLUENZA vaccines, ANTIGENS, LABORATORY mice, ADENOVIRUSES, BONOBO, DISEASE vectors, TRANSGENES, NUCLEOPROTEINS, DISEASES
Abstract

Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. [ABSTRACT FROM AUTHOR]

Published
2013
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28. Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus.

Author

Vitelli, Alessandra, Quirion, Mary R., Lo, Chia-Yun, Misplon, Julia A., Grabowska, Agnieszka K., Pierantoni, Angiolo, Ammendola, Virginia, Price, Graeme E., Soboleski, Mark R., Cortese, Riccardo, Colloca, Stefano, Nicosia, Alfredo, and Epstein, Suzanne L.

Subjects
*INFLUENZA vaccines, *ANTIGENS, *LABORATORY mice, *ADENOVIRUSES, *BONOBO, *DISEASE vectors, *TRANSGENES, *NUCLEOPROTEINS, *DISEASES
Abstract

Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. [ABSTRACT FROM AUTHOR]

Published
2013
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29. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

Author

Angiolo Pierantoni1, Maria Luisa Esposito1, Virginia Ammendola1, Federico Napolitano1, Fabiana Grazioli1, Adele Abbate1, Mariarosaria del Sorbo1, Loredana Siani1, Anna Morena D'Alise1, Alessandra Taglioni3, Gemma Perretta3, Antonio Siccardi4, Elisa Soprana4, Maddalena Panigada4, Michelle Thom2, Elisa Scarselli1, Antonella Folgori1, Stefano Colloca1, Geraldine Taylor2, Riccardo Cortese1, 7, Alfredo Nicosia1, 5, 6, Stefania Capone1, Alessandra Vitelli1, Pierantoni, Angiolo, Esposito, Maria Luisa, Ammendola, Virginia, Napolitano, Federico, Grazioli, Fabiana, Abbate, Adele, del Sorbo, Mariarosaria, Siani, Loredana, D'Alise, Anna Morena, Taglioni, Alessandra, Perretta, Gemma, Siccardi, Antonio, Soprana, Elisa, Panigada, Maddalena, Thom, Michelle, Scarselli, Elisa, Folgori, Antonella, Colloca, Stefano, Taylor, Geraldine, Cortese, Riccardo, Nicosia, Alfredo, Capone, Stefania, and Vitelli, Alessandra

Subjects
Cellular immunity, Modified vaccinia Ankara, lcsh:QH426-470, viruses, Virus, Article, Lower respiratory tract infection, medicine, Genetics, lcsh:QH573-671, Neutralizing antibody, Molecular Biology, biology, business.industry, lcsh:Cytology, Immunogenicity, virus diseases, respiratory system, medicine.disease, Virology, 3. Good health, Vaccination, lcsh:Genetics, medicine.anatomical_structure, Immunology, biology.protein, Molecular Medicine, business, Respiratory tract
Abstract

Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.

Published
2015

30. Combined adenovirus vector and hepatitis C virus envelope protein prime-boost regimen elicits T cell and neutralizing antibody immune responses

Author

Alicja M Chmielewska, Stefano Colloca, Philip Meuleman, Rino Rappuoli, Jane A. McKeating, Lieven Verhoye, Ke Hu, Virginia Ammendola, Riccardo Cortese, Krystyna Bieńkowska-Szewczyk, Jeffrey B. Ulmer, Antonella Folgori, M. Naddeo, Luke W. Meredith, Alfredo Nicosia, Geert Leroux-Roels, Peter Balfe, Stefania Capone, Małgorzata Rychłowska, Chmielewska, Alicja M., Naddeo, Mariarosaria, Capone, Stefania, Ammendola, Virginia, Hu, Ke, Meredith, Luke, Verhoye, Lieven, Rychlowska, Malgorzata, Rappuoli, Rino, Ulmer, Jeffrey B., Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, Leroux Roels, Geert, Balfe, Peter, Bienkowska Szewczyk, Krystyna, Meuleman, Philip, Mckeating, Jane A., and Folgori, Antonella

Subjects
T-Lymphocytes, Polysorbates, Hepacivirus, Mice, Viral Envelope Proteins, Neutralizing antibody, Mice, Inbred BALB C, Vaccines, Synthetic, Viral Vaccine, Vaccination, Viral Envelope Protein, Polysorbate, Adenovirus vaccine, medicine.anatomical_structure, Female, Genetic Vector, medicine.drug, Squalene, T cell, Recombinant Fusion Proteins, Immunology, Genetic Vectors, Guinea Pigs, Biology, Microbiology, Guinea Pig, DNA vaccination, Viral vector, Adenoviridae, Antigen, Adjuvants, Immunologic, Virology, Vaccines and Antiviral Agents, medicine, Animals, Hepaciviru, Animal, Viral Vaccines, Hepatitis C Antibodies, Antibodies, Neutralizing, Mice, Inbred C57BL, T-Lymphocyte, Insect Science, biology.protein, Hepatitis C Antibodie, Recombinant Fusion Protein
Abstract

Despite the recent progress in the development of new antiviral agents, hepatitis C virus (HCV) infection remains a major global health problem, and there is a need for a preventive vaccine. We previously reported that adenoviral vectors expressing HCV nonstructural proteins elicit protective T cell responses in chimpanzees and were immunogenic in healthy volunteers. Furthermore, recombinant HCV E1E2 protein formulated with adjuvant MF59 induced protective antibody responses in chimpanzees and was immunogenic in humans. To develop an HCV vaccine capable of inducing both T cell and antibody responses, we constructed adenoviral vectors expressing full-length and truncated E1E2 envelope glycoproteins from HCV genotype 1b. Heterologous prime-boost immunization regimens with adenovirus and recombinant E1E2 glycoprotein (genotype 1a) plus MF59 were evaluated in mice and guinea pigs. Adenovirus prime and protein boost induced broad HCV-specific CD8 + and CD4 + T cell responses and functional Th1-type IgG responses. Immune sera neutralized luciferase reporter pseudoparticles expressing HCV envelope glycoproteins (HCVpp) and a diverse panel of recombinant cell culture-derived HCV (HCVcc) strains and limited cell-to-cell HCV transmission. This study demonstrated that combining adenovirus vector with protein antigen can induce strong antibody and T cell responses that surpass immune responses achieved by either vaccine alone. IMPORTANCE HCV infection is a major health problem. Despite the availability of new directly acting antiviral agents for treating chronic infection, an affordable preventive vaccine provides the best long-term goal for controlling the global epidemic. This report describes a new anti-HCV vaccine targeting the envelope viral proteins based on adenovirus vector and protein in adjuvant. Rodents primed with the adenovirus vaccine and boosted with the adjuvanted protein developed cross-neutralizing antibodies and potent T cell responses that surpassed immune responses achieved with either vaccine component alone. If combined with the adenovirus vaccine targeting the HCV NS antigens now under clinical testing, this new vaccine might lead to a stronger and broader immune response and to a more effective vaccine to prevent HCV infection. Importantly, the described approach represents a valuable strategy for other infectious diseases in which both T and B cell responses are essential for protection.

Published
2014

31. A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory

Author

Rachel Richardson, Loredana Siani, Antonella Folgori, Riccardo Cortese, Evan W. Newell, Joannah R. Fergusson, Fabiana Grazioli, Cinzia Traboni, Alfredo Nicosia, Mark M. Davis, Adrian V. S. Hill, Leo Swadling, Maria Luisa Esposito, Richard D Antrobus, Dan Hameiri Bowen, Stefania Capone, John Halliday, Virginia Ammendola, Eleanor Barnes, Christabel Kelly, Anthony Brown, Mariarosaria Del Sorbo, Stefano Colloca, Ayako Kurioka, Paul Klenerman, Swadling, Leo, Capone, Stefania, Antrobus, Richard D., Brown, Anthony, Richardson, Rachel, Newell, Evan W., Halliday, John, Kelly, Christabel, Bowen, Dan, Fergusson, Joannah, Kurioka, Ayako, Ammendola, Virginia, Del Sorbo, Mariarosaria, Grazioli, Fabiana, Esposito, Maria Luisa, Siani, Loredana, Traboni, Cinzia, Hill, Adrian, Colloca, Stefano, Davis, Mark, Nicosia, Alfredo, Cortese, Riccardo, Folgori, Antonella, Klenerman, Paul, and Barnes, Eleanor

Subjects
CD4-Positive T-Lymphocytes, Modified vaccinia Ankara, Enzyme-Linked Immunospot Assay, Time Factors, viruses, Hepacivirus, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Interferon-gamma Release Test, Vaccines, DNA, Vector (molecular biology), Cells, Cultured, Viral Vaccine, Medicine (all), Pan troglodyte, Vaccination, virus diseases, General Medicine, Healthy Volunteer, Hepatitis C, Healthy Volunteers, medicine.anatomical_structure, Treatment Outcome, England, CD4-Positive T-Lymphocyte, Human, Viral Hepatitis Vaccines, Pan troglodytes, Time Factor, T cell, Biology, Article, Viral vector, Adenoviridae, Antigen, medicine, Animals, Humans, Cell Proliferation, Hepaciviru, Animal, Histocompatibility Antigens Class I, Viral Vaccines, CD8-Positive T-Lymphocyte, biochemical phenomena, metabolism, and nutrition, Hepatitis C Antibodies, Virology, digestive system diseases, Immunology, Hepatitis C Antibodie, Immunologic Memory, Interferon-gamma Release Tests, CD8, Viral Hepatitis Vaccine
Abstract

A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies, and assessment of host immunity during acute infection highlight the critical role that effective T cell immunity plays in viral control. In this first-in-man study, we have induced antiviral immunity with functional characteristics analogous to those associated with viral control in natural infection, and improved upon a vaccine based on adenoviral vectors alone. We assessed a heterologous prime-boost vaccination strategy based on a replicative defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA) vector encoding the NS3, NS4, NS5A, and NS5B proteins of HCV genotype 1b. Analysis used single-cell mass cytometry and human leukocyte antigen class I peptide tetramer technology in healthy human volunteers. We show that HCV-specific T cells induced by ChAd3 are optimally boosted with MVA, and generate very high levels of both CD8(+) and CD4(+) HCV-specific T cells targeting multiple HCV antigens. Sustained memory and effector T cell populations are generated, and T cell memory evolved over time with improvement of quality (proliferation and polyfunctionality) after heterologous MVA boost. We have developed an HCV vaccine strategy, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.

Published
2014

32. Fusion of HCV non-structural antigen to MHC Class II associated invariant chain enhances T cell responses induced by vectored vaccines in non-human primates

Author

Stefania Capone 1, Mariarosaria Naddeo 1, Anna Morena D'Alise 1, Adele Abbate 1, Fabiana Grazioli 1, Annunziata Del Gaudio 1, Mariarosaria del Sorbo 1, Maria Luisa Esposito 1, Virginia Ammendola 1, Gemma Perretta 2, Alessandra Taglioni 2, Stefano Colloca 1, Alfredo Nicosia 1, 3, 4, Riccardo Cortese 1, 5, Antonella Folgori 1, Capone, Stefania, Naddeo, Mariarosaria, D'Alise, Anna Morena, Abbate, Adele, Grazioli, Fabiana, Del Gaudio, Annunziata, Del Sorbo, Mariarosaria, Esposito, Maria Luisa, Ammendola, Virginia, Perretta, Gemma, Taglioni, Alessandra, Colloca, Stefano, Nicosia, Alfredo, Cortese, Riccardo, and Folgori, Antonella

Subjects
Modified vaccinia Ankara, Hepacivirus, CD8-Positive T-Lymphocytes, Mice, 0302 clinical medicine, Drug Discovery, Antigens, Viral, Vaccines, 0303 health sciences, Medicine (all), Immunogenicity, Pan troglodyte, Hepatitis C, 3. Good health, Adenovirus vaccine, medicine.anatomical_structure, Molecular Medicine, Original Article, Human, medicine.drug, Pan troglodytes, Recombinant Fusion Proteins, T cell, Genes, MHC Class II, Biology, Major histocompatibility complex, Adenoviridae, Viral vector, Interferon-gamma, 03 medical and health sciences, Genetic, Antigen, Genetics, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, Pharmacology, Hepaciviru, Animal, Drug Discovery3003 Pharmaceutical Science, Histocompatibility Antigens Class II, CD8-Positive T-Lymphocyte, Virology, Antigens, Differentiation, B-Lymphocyte, Immunology, biology.protein, Vaccine, CD8, Recombinant Fusion Protein, 030215 immunology
Abstract

Despite viral vectors being potent inducers of antigen-specific T cells, strategies to further improve their immunogenicity are actively pursued. Of the numerous approaches investigated, fusion of the encoded antigen to major histocompatibility complex class II-associated invariant chain (Ii) has been reported to enhance CD8(+) T-cell responses. We have previously shown that adenovirus vaccine encoding nonstructural (NS) hepatitis C virus (HCV) proteins induces potent T-cell responses in humans. However, even higher T-cell responses might be required to achieve efficacy against different HCV genotypes or therapeutic effect in chronically infected HCV patients. In this study, we assessed fusion of the HCV NS antigen to murine and human Ii expressed by the chimpanzee adenovirus vector ChAd3 or recombinant modified vaccinia Ankara in mice and nonhuman primates (NHPs). A dramatic increase was observed in outbred mice in which vaccination with ChAd3 expressing the fusion antigen resulted in a 10-fold increase in interferon-γ(+) CD8(+) T cells. In NHPs, CD8(+) T-cell responses were enhanced and accelerated with vectors encoding the Ii-fused antigen. These data show for the first time that the enhancement induced by vector vaccines encoding li-fused antigen was not species specific and can be translated from mice to NHPs, opening the way for testing in humans.

Published
2014
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33. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge

Author

Annie W. Lau-Kilby, Cheng Cheng, Nancy J. Sullivan, Joshua C. Johnson, Clement Asiedu, John C. Trefry, Lingshu Wang, Antonella Folgori, Alfredo Nicosia, Adele Abbate, Kathryn E. Foulds, Richard A. Koup, Fabiana Grazioli, Riccardo Cortese, Gary J. Nabel, Mario Roederer, Daphne A. Stanley, Anna N. Honko, Stefano Colloca, Mitzi M. Donaldson, Lisa E. Hensley, John R. Mascola, Virginia Ammendola, Stanley, Daphne A, Honko, Anna N., Asiedu, Clement, Trefry, John C., Lau Kilby, Annie W., Johnson, Joshua C., Hensley, Lisa, Ammendola, Virginia, Abbate, Adele, Grazioli, Fabiana, Foulds, Kathryn E., Cheng, Cheng, Wang, Lingshu, Donaldson, Mitzi M., Colloca, Stefano, Folgori, Antonella, Roederer, Mario, Nabel, Gary J., Mascola, John, Nicosia, Alfredo, Cortese, Riccardo, Koup, Richard A., and Sullivan, Nancy J.

Subjects
Protective immunity, Time Factors, Pan troglodytes, Time Factor, Genetic Vectors, Immunization, Secondary, Chimpanzee adenovirus, Vaccinia virus, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Ebolaviru, Adenovirus Vaccines, medicine, Animals, Humans, Defective Viruse, Ebola Vaccine, Ebola Vaccines, Macaca fasciculari, Ebolavirus, Biochemistry, Genetics and Molecular Biology (all), Ebola vaccine, Animal, Adenoviruses, Human, Medicine (all), Pan troglodyte, Defective Viruses, General Medicine, Hemorrhagic Fever, Ebola, Virology, Vaccinia viru, Vaccination, Macaca fascicularis, Adenovirus Vaccine, Immunology, Adenoviruses, Simian, RNA, Viral, Female, Genetic Vector, Human
Abstract

Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge.

Published
2014

34. MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans.

Author

Esposito I, Cicconi P, D'Alise AM, Brown A, Esposito M, Swadling L, Holst PJ, Bassi MR, Stornaiuolo M, Mori F, Vassilev V, Li W, Donnison T, Gentile C, Turner B, von Delft A, Del Sorbo M, Barra F, Contino AM, Abbate A, Novellino E, Thomsen AR, Christensen JP, Lahm A, Grazioli F, Ammendola V, Siani L, Colloca S, Klenerman P, Nicosia A, Dorrell L, Folgori A, Capone S, and Barnes E

Subjects
Antigens, Differentiation, B-Lymphocyte genetics, CD8-Positive T-Lymphocytes, Hepacivirus genetics, Histocompatibility Antigens Class II, Humans, Viral Vaccines
Abstract

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4 + T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8 + and CD4 + responses were induced with up to 30% of CD3 + CD8 + cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Published
2020
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35. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.

Author

Pierantoni A, Esposito ML, Ammendola V, Napolitano F, Grazioli F, Abbate A, Del Sorbo M, Siani L, D'Alise AM, Taglioni A, Perretta G, Siccardi A, Soprana E, Panigada M, Thom M, Scarselli E, Folgori A, Colloca S, Taylor G, Cortese R, Nicosia A, Capone S, and Vitelli A

Abstract

Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing.

Published
2015
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