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


Capone, Stefania, Raggioli, Angelo, Gentile, Michela, Battella, Simone, Lahm, Armin, Sommella, Andrea, Contino, Alessandra Maria, Urbanowicz, Richard A ORCID: 0000-0002-2461-4993, Scala, Romina, Barra, Federica et al (show 18 more authors) (2021) Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19. MOLECULAR THERAPY, 29 (8). pp. 2412-2423.

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Abstract

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).

Item Type: Article
Uncontrolled Keywords: Cell Line, Cell Line, Tumor, Hela Cells, Animals, Mice, Inbred BALB C, Macaca, Gorilla gorilla, Humans, Mice, Adenoviridae, Antibodies, Viral, Genetic Vectors, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Antibodies, Neutralizing, HEK293 Cells, Pandemics, Adenovirus Vaccines, Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 12 May 2021 10:33
Last Modified: 18 Jan 2023 22:49
DOI: 10.1016/j.ymthe.2021.04.022
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3121878
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