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

被引:42
|
作者
Capone, Stefania [1 ]
Raggioli, Angelo [1 ]
Gentile, Michela [1 ]
Battella, Simone [1 ]
Lahm, Armin [1 ]
Sommella, Andrea [1 ]
Contino, Alessandra Maria [1 ]
Urbanowicz, Richard A. [2 ,3 ,4 ,6 ]
Scala, Romina [1 ]
Barra, Federica [1 ]
Leuzzi, Adriano [1 ]
Lilli, Eleonora [1 ]
Miselli, Giuseppina [1 ]
Noto, Alessia [1 ]
Ferraiuolo, Maria [1 ]
Talotta, Francesco [1 ]
Tsoleridis, Theocharis [2 ,3 ,4 ]
Castilletti, Concetta [5 ]
Matusali, Giulia [5 ]
Colavita, Francesca [5 ]
Lapa, Daniele [5 ]
Meschi, Silvia [5 ]
Capobianchi, Maria [5 ]
Soriani, Marco [1 ]
Folgori, Antonella [1 ]
Ball, Jonathan K. [2 ,3 ,4 ]
Colloca, Stefano [1 ]
Vitelli, Alessandra [1 ]
机构
[1] ReiThera Srl, Via Castel Romano 100, I-00128 Rome, Italy
[2] Univ Nottingham, Sch Life Sci, Nottingham, England
[3] Univ Nottingham, NIHR Nottingham Biomed Res Ctr, Nottingham, England
[4] Univ Nottingham, Wolfson Ctr Emerging Virus Res, Nottingham, England
[5] Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Rome, Italy
[6] Univ Liverpool, Inst Infect Vet & Ecol Sci, Liverpool, Merseyside, England
基金
英国医学研究理事会; 欧盟地平线“2020”;
关键词
DESIGN; GENE;
D O I
10.1016/j.ymthe.2021.04.022
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:2412 / 2423
页数:12
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