Immunogenicity of a new gorilla adenovirus vaccine candidate for COVID-19.
Mol Ther
; 29(8): 2412-2423, 2021 08 04.
Article
en En
| MEDLINE
| ID: mdl-33895322
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).
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Adenoviridae
/
Vacunas contra el Adenovirus
/
Inmunogenicidad Vacunal
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Vacunas contra la COVID-19
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SARS-CoV-2
/
COVID-19
/
Gorilla gorilla
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
/
Adult
/
Aged
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Aged80
/
Animals
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mol Ther
Asunto de la revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia