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.
【저자키워드】 immune response, variants of concern, COVID vaccine, hybrid adenovirus vector, 【초록키워드】 COVID-19, SARS-CoV-2, Vaccine, spike, antibody, Infection, B.1.617.2, clinical trials, monocyte, Adenovirus, Humoral immunity, cells, pseudovirus, mice, mRNA, P.1, D614G, Alpha, expression, wild type, immunodominance, dendritic cell, single dose, T-cell immunity, B.1, chimeric, regimen, domain, promoter, MOST, prefusion conformation, Administered, fiber, neutralize, ENhance, approved, expressed, expressing, replacing, the Spike, 【제목키워드】 VoC, response, hybrid,