TY - JOUR
T1 - Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19
AU - Capone, Stefania
AU - Raggioli, Angelo
AU - Gentile, Michela
AU - Battella, Simone
AU - Lahm, Armin
AU - Sommella, Andrea
AU - Contino, Alessandra Maria
AU - Urbanowicz, Richard A.
AU - Scala, Romina
AU - Barra, Federica
AU - Leuzzi, Adriano
AU - Lilli, Eleonora
AU - Miselli, Giuseppina
AU - Noto, Alessia
AU - Ferraiuolo, Maria
AU - Talotta, Francesco
AU - Tsoleridis, Theocharis
AU - Castilletti, Concetta
AU - Matusali, Giulia
AU - Colavita, Francesca
AU - Lapa, Daniele
AU - Meschi, Silvia
AU - Capobianchi, Maria
AU - Soriani, Marco
AU - Folgori, Antonella
AU - Ball, Jonathan
AU - Colloca, Stefano
AU - Vitelli, Alessandra
PY - 2021/8/4
Y1 - 2021/8/4
N2 - 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 (ClinicalTrials.gov: NCT04528641).
AB - 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 (ClinicalTrials.gov: NCT04528641).
KW - COVID-19
KW - gorilla adenovirus
KW - immunogenicity
KW - SARS-CoV-2
KW - vaccine
U2 - 10.1016/j.ymthe.2021.04.022
DO - 10.1016/j.ymthe.2021.04.022
M3 - Article
SN - 1525-0016
VL - 29
SP - 2412
EP - 2423
JO - Molecular Therapy
JF - Molecular Therapy
IS - 8
ER -
