A single shot 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.; Nuñez, Felipe J.; Soto, Ariadna; Sanchez-Lamas, Maximiliano; Afonso, Jimena; Aguilar-Cortes, Diana; Ríos, Gregorio D.; Maricato, Juliana T.; Torres-Braconi, Carla; Silveira, Vanessa Barbosa-da; Montes-de Andrade, Tatiane; Carvalho-de Souza Bonetti, Tatiana; Ramos Janini, Luiz M.; Castello Girão, Manoel J. B.; Llera, Andrea S.; Gomez, Karina; 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 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 a 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. Transduction with CoroVaxG.3 expressing Spike (D614G) dramatically enhanced 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 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) and P.1 (gamma) Spikes, as well as an authentic WT and P.1 SARS-CoV-2 isolates. Neutralizing antibodies did not wane even after 5 months making this kind of vaccine a likely candidate to enter clinical trials