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

EDUARDO G CAFFERATA; MAXIMILIANO SANCHEZ-LAMAS; GREGORIO D. RÍOS; VANESSA BARBOSA-DA SILVEIRA; LUIZ M. RAMOS JANINI; KARINA GOMEZ; OSVALDO L. PODHAJCER ; M VERONICA LOPEZ; FELIPE J. NUÑEZ1; M JIMENA AFONSO; JULIANA T MARICATO; TATIANE MONTES-DE ANDRADE; MANOEL J. B. CASTELLO GIRÃO; HUGO H. ORTEGA; SABRINA E VINZON; ARIADNA SOTO; DIANA AGUILAR-CORTES; CARLA TORRES-BRACONI; TATIANA CARVALHO-DE SOUZA BONETTI; ANDREA S. LLERA; PAULA M. BERGUER

Vaccines

MDPI

Lugar: Basel; Año: 2021 vol. 9

2076-393X

Most approved vaccines against COVID-19 have to be administered in a prime/boostregimen. 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 itsimmunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection ofmuscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spikestabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G)dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cellscompared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3induced 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 neutralizepseudoviruses 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 evenafter 5 months, making this kind of vaccine a likely candidate to enter clinical trials.