A single dose of a hybrid hadv5-based anti-covid-19 vaccine induces a long-lasting immune response and broad coverage against voc

CAFFERATA, EDUARDO G. A.; SANCHEZ-LAMAS, MAXIMILIANO; RÍOS, GREGORIO D.; SILVEIRA, VANESSA BARBOSA-DA; RAMOS JANINI, LUIZ M.; GOMEZ, KARINA A.; PODHAJCER, OSVALDO L.; VINZÓN, SABRINA E.; SOTO, ARIADNA; AGUILAR-CORTES, DIANA; TORRES-BRACONI, CARLA; BONETTI, TATIANA CARVALHO-DE SOUZA; LLERA, ANDREA S.; BERGUER, PAULA M.; VERÓNICA LÓPEZ, M.; NUÑEZ, FELIPE J.; JIMENA AFONSO, M.; MARICATO, JULIANA T.; ANDRADE, TATIANE MONTES-DE; CASTELLO GIRÃO, MANOEL J. B.; ORTEGA, HUGO H.

Vaccines

MDPI

Año: 2021 vol. 9

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.