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

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.

Automated summary

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.