GRAd-COV2 vaccine provides potent and durable humoral and cellular immunity to SARS-CoV-2 in randomized placebo-controlled phase 2 trial
Stefania Capone, Francesco Maria Fusco, Stefano Milleri, Silvio Borrè, Sergio Carbonara, Sergio Lo Caputo, Sebastiano Leone, Giovanni Gori, Paolo Maggi, Antonio Cascio, Miriam Lichtner, Roberto Cauda, Sarah Dal Zoppo, Maria Vittoria Cossu, Andrea Gori, Silvia Roda, Paola Confalonieri, Stefano Bonora, Gabriele Missale, Mauro Codeluppi, Ivano Mezzaroma, Serena Capici, Emanuele Pontali, Marco Libanore, Augusta Diani, Simone Lanini, Simone Battella, Alessandra M. Contino, Eva Piano Mortari, Francesco Genova, Gessica Parente, Rosella Dragonetti, Stefano Colloca, Luigi Visani, Claudio Iannacone, Rita Carsetti, Antonella Folgori, Roberto Camerini, Luigi Ziviani, Feliciana Malescio, Irene Turrini, Rita T. Lawlor, Annamaria Romano, Mariagrazia Nunziata, Salvatore Armato, Nicole Mazzeo, Maria Aurora Carleo, Chiara Dell’Isola, Raffaella Pisapia, Agostina Pontarelli, Andrea Olivani, Sara Grasselli, Diletta Laccabue, Maria Cristina Leone, F Paolillo, Annalisa Mancini, Barbara Ruaro, Marco Confalonieri, Francesco Salton, Giulia Mancarella, Raffaella Marocco, Margherita De Masi, Valeria Belvisi, Silvia Lamonica, Antonella Cingolani, Cristina Seguiti, Paola Brambilla, Alice Ferraresi, Matteo Lupi, Serena Ludovisi, Giulia Renisi, Roberta Massafra, Martina Pellicciotta, Luciana Armiento, Stefania Vimercati, M Piacenza, Paolo Bonfanti, Paola Columpsi, Marina Elena Cazzaniga, Cristina Rovelli, Mariaelena Ceresini, Letizia Previtali, L. Trentini, Chiara Alcantarini, Walter Rugge, Stefano Biffi, Federica Poletti, Roberto Rostagno, Roberta Moglia, Ferdinando De Negri, Elisabetta Fini, Alice Cangialosi, Serena Rita Bruno, Marianna Rizzo, Mariangela Niglio, Anna Dello Stritto, A Matano, Arnolfo Petruzziello, Pietro Valsecchi, Teresa Chiara Pieri
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 (COVITAR study, 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.