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López, M Verónica; Vinzón, Sabrina E; Cafferata, Eduardo G A; Núñez, Felipe J; Soto, Ariadna; Sanchez-Lamas, Maximiliano; Afonso, M Jimena; Aguilar-Cortes, Diana; Ríos, Gregorio D; Maricato, Juliana T; Braconi, Carla T; Silveira, Vanessa B; Andrad, Tatiane M; Bonetti, Tatiana C S; Ramos Janini, Luiz M; Girão, Manoel J B C; Llera, Andrea S; Gomez, Karina A; Ortega, Hugo H; Berguer, Paula M; Podhajcer, Osvaldo L
Vaccines (Basel), 09/2021, Volume: 9, Issue: 10Journal Article
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.
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