A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC
| Autor: | Tatiana C.S. Bonetti, Eduardo G. Cafferata, Maximiliano Sanchez-Lamas, Luiz Mario Janini, Karina A. Gómez, M. Veronica Lopez, Manoel João Batista Castello Girão, Andrea S. Llera, Juliana Terzi Maricato, Vanessa B Silveira, Felipe J Nunez, Gregorio D Ríos, Carla Torres Braconi, Diana Aguilar-Cortes, M Jimena Afonso, Hugo Hector Ortega, Paula Mercedes Berguer, Ariadna Soto, Sabrina E. Vinzón, Osvaldo L. Podhajcer, Tatiane M Andrad |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
hybrid adenovirus vector Immunology Wild type Immunodominance Biology COVID vaccine variants of concern Virology Article immune response Transduction (genetics) Infectious Diseases Immune system Immunity Drug Discovery Humoral immunity biology.protein Medicine Pharmacology (medical) Vector (molecular biology) Antibody |
| Zdroj: | Vaccines Vaccines, Vol 9, Iss 1106, p 1106 (2021) Volume 9 Issue 10 |
| ISSN: | 2076-393X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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