A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC

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.; T. Braconi, Carla; B. Silveira, Vanessa; M. Andrad, Tatiane; C. S. Bonetti, Tatiana; Ramos Janini, Luiz M.; Girão, Manoel J. B. C.; Llera, Andrea S.; Gomez, Karina A.; Ortega, Hugo H.; Berguer, Paula M.; Podhajcer, Osvaldo L.

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.