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

• DOI: 10.1016/j.xcrm.2023.101084
• Publication Date: 2023-05-29T08:18:58Z
• Authors: Stefania Capone; Francesco M. 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 V. 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. Con...; 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 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 Leoni; Franco 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; Mariagrazia Piacenza; Paolo Bonfanti; Paola Columpsi; Marina Elena Cazz...; Cristina Rovelli; Mariaelena Ceresini; Letizia Previtali; Laura 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; Alfredo Matano; Arnolfo Petruzziello; Pietro Valsecchi; Teresa Pieri; Mauro Altamura; Angela Calamo; Anna Giannelli; Stefania Menolascina; Silvia Di Bari; Vera Mauro; Raissa Aronica; Daniela Segala; Rosario Cultrera; Laura Sighinolfi; Michelle Abbott; Andrea Gizzi; Federica Guida Ma...; Giacomo Valenti; Marcello Feasi; Nicoletta Bobbio; Filippo Del Puente; Alfredo Nicosia; Martina Frascà; Miriam Mazzoleni; Nadia Garofalo; Virginia Ammendola; Fabiana Grazioli; Federico Napolitano; Alessandra Vitelli; Valentina Marcellini
• Keywords: safety; CD4, CD8, COVID-19, Sars-CoV-2 vaccine, T cell response, immunological memory, neutralizing antibodies, phase 2 clinical trial, safety, simian adenoviral vector,.; Vaccines; Immunity, Cellular; cd4; cd8; covid-19; sars-cov-2 vaccine; t cell response; immunological memory; neutralizing antibodies; phase 2 clinical trial; safety; simian adenoviral vector; COVID-19 Vaccines; SARS-CoV-2; simian adenoviral vector.; COVID-19; CD8; CD4; CD8; COVID-19; Sars-CoV-2 vaccine; T cell response; immunological memory; neutralizing antibodies; phase 2 clinical trial; safety; simian adenoviral vector; T cell response; CD4; Article; 3. Good health; neutralizing antibodie; immunological memory; phase 2 clinical trial; Sars-CoV-2 vaccine; CD4; CD8; COVID-19; Sars-CoV-2 vaccine; T cell response; immunological memory; neutralizing antibodies; phase 2 clinical trial; safety; simian adenoviral vector.; Humans; neutralizing antibodies; CD4; CD8; COVID-19; immunological memory; neutralizing antibodies; phase 2 clinical trial; safety; Sars-CoV-2 vaccine; simian adenoviral vector; T cell response;; simian adenoviral vector; immunological memory, simian adenoviral vector, safety, phase 2 clinical trial, COVID-19, CD4, CD8, Sars-CoV-2 vaccine, T cell response, neutralizing antibodies

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.