A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC.
M Verónica LópezSabrina E VinzónEduardo G A CafferataFelipe J NúñezAriadna SotoMaximiliano Sánchez-LamasM Jimena AfonsoDiana Aguilar-CortesGregorio D RíosJuliana T MaricatoCarla Torres BraconiVanessa B SilveiraTatiane M AndradTatiana Carvalho de Souza BonettiLuiz M Ramos JaniniManoel J B C GirãoAndrea Sabina LleraKarina A GomezHugo H OrtegaPaula M BerguerOsvaldo L PodhajcerPublished in: Vaccines (2021)
Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.
Keyphrases
- dendritic cells
- immune response
- sars cov
- wild type
- endothelial cells
- coronavirus disease
- clinical trial
- poor prognosis
- regulatory t cells
- skeletal muscle
- respiratory syndrome coronavirus
- high glucose
- induced apoptosis
- binding protein
- anti inflammatory
- dna methylation
- stem cells
- pluripotent stem cells
- cell therapy
- gene expression
- adipose tissue
- open label
- type diabetes
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- crystal structure
- dengue virus