A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC

Lopez, M. V.; Vinzon, S. E.; Cafferata, E. G. A.; Nunez, F. J.; Soto, A.; Sanchez-Lamas, M.; Afonso, J.; Aguilar-Cortes, D.; Rios, G. D.; Maricato, J. T.; Torres-Braconi, C.; Barbosa-da Silveira, V.; Montes-de Andrade, T.; Carvalho-de Souza Bonetti, T.; Ramos Janini, L. M.; Castello Girao, M. J. B.; Llera, A. S.; Gomez, K.; Hortega, H. H.; Berguer, P. M.; Podhajcer, O. L.

doi:10.1101/2021.08.11.455942

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bioRxiv · 10.1101/2021.08.11.455942

A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC

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Abstract

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

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Lopez, M. V., Vinzon, S. E., Cafferata, E. G. A., Nunez, F. J., Soto, A., Sanchez-Lamas, M., Afonso, J., Aguilar-Cortes, D., Rios, G. D., Maricato, J. T., Torres-Braconi, C., Barbosa-da Silveira, V., Montes-de Andrade, T., Carvalho-de Souza Bonetti, T., Ramos Janini, L. M., Castello Girao, M. J. B., Llera, A. S., Gomez, K., Hortega, H. H., Berguer, P. M., Podhajcer, O. L.. 2021-08-11. A single shot of a hybrid hAdV5-based anti-COVID-19 vaccine induces a long-lasting immune response and broad coverage against VOC. https://doi.org/10.1101/2021.08.11.455942

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