Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19

Originally published on Molecular Therapy Volume 29, Issue 8, 4 August 2021, Pages 2412-2423

  • Stefania Capone, Angelo Raggioli, Michela Gentile, Simone Battella, Armin Lahm, Andrea Sommella, Alessandra Maria Contino, Richard A. Urbanowicz, Romina Scala, Federica Barra, Adriano, Leuzzi, Eleonora Lilli, Giuseppina Miselli, Alessia Noto, Maria Ferraiuolo, Francesco Talotta, Theocharis Tsoleridis, Concetta Castilletti, Giulia Matusali, Francesca Colavita, Daniele Lapa, Silvia Meschi, Maria Capobianchi, Marco Soriani, Antonella Folgori, Jonathan K.Ball, Stefano Colloca, Alessandra Vitelli

The coronavirus disease 2019 (COVID-19) pandemic caused by the emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health, and there is an urgent need to develop safe and effective vaccines. Here, we report the generation and the preclinical evaluation of a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike (S) protein of SARS-CoV-2. We show that our vaccine candidate, GRAd-COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies that neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, T helper (Th)1-dominated cellular response. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV-2-neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at a massive scale, different GRAd genome deletions were compared to select the vector backbone showing the highest productivity in stirred tank bioreactors. This preliminary dataset identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting the translation of the GRAd-COV2 vaccine in a currently ongoing phase I clinical trial ( NCT04528641).