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.V.; VINZÓN, S.E; CAFFERATA, E.G.A; NÚÑEZ, F.J; SOTO, A; SANCHEZ-LAMAS, M.; AFONSO, M.J; AGUILAR-CORTES, D.; RÍOS, G.D.; MARICATO, J.T.; BRACONI, C.T.; SILVEIRA, V.B.; ANDRAD, T.M.; BONETTI, T.C.S.; RAMOS JANINI, L.M.; GIRÃO, M.J.B.C.; LLERA, A.S.; GOMEZ, K.A.; ORTEGA, H.H.; BERGUER, P.M.; PODHAJCER, O.L.

Vaccines

MDPI

Lugar: Basel; Año: 2021

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.