Paper

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

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

2020

Overview

ABSTRACT The COVID-19 pandemic caused by the emergent SARS-CoV-2 coronavirus 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-CoV2. We show that our vaccine candidate, GRAd- COV2, is highly immunogenic both in mice and macaques, eliciting both functional antibodies which neutralize SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and a robust, Th1- dominated cellular response in the periphery and in the lung. We show here that the pre-fusion stabilized Spike antigen is superior to the wild type in inducing ACE2-interfering, SARS-CoV2 neutralizing antibodies. To face the unprecedented need for vaccine manufacturing at 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 GRAd-COV2 vaccine in a currently ongoing Phase I clinical trial (NCT04528641). Competing Interest Statement The authors have declared no competing interest.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: ACE2 / Adenoviruses / Angiotensin-converting enzyme 2 / Antibodies / Bioreactors / Coronaviruses / COVID-19 / COVID-19 vaccines / Fusion protein / Genomes / Immunogenicity / Immunology / Lymphocytes T / Pandemics / Public health / Severe acute respiratory syndrome coronavirus 2 / Spike protein / Vaccines