Journal
MOLECULAR THERAPY
Volume 29, Issue 8, Pages 2412-2423Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2021.04.022
Keywords
-
Categories
Funding
- Medical Research Council UK, EDCTP2 Programme - European Union [MR/R010307/1, MR/S009434/1]
- University of Nottingham Campaign
- Alumni Relations Office Research Donations Award
- EU H2020 Programme [727393-PaleBlu]
- Lazio Region, Italian Ministry of Research-National Research Council
- National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS from the Italian Ministry of Health [COVID-2020-12371817]
- European Commission-European Virus Archive-GLOBAL [653316, 871029]
Ask authors/readers for more resources
The study introduced a novel replication-defective gorilla adenovirus-vectored vaccine encoding the pre-fusion stabilized Spike protein of SARS-CoV-2, which showed high immunogenicity in mice and macaques. The research highlighted the superiority of the pre-fusion stabilized Spike antigen in inducing ACE2-interfering, SARS-CoV-2-neutralizing antibodies. Selection of the vector backbone and preliminary data identified GRAd-COV2 as a potential COVID-19 vaccine candidate, supporting its translation into a phase I clinical trial.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available