A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC

Vaccines

Hugo H. Ortega¹  Manoel J. B. C. Girão²  Tatiana C. S.Bonetti²  Juliana T. Maricato³  Luiz M. Ramos Janini³  Vanessa B.Silveira³  Tatiane M. Andrad³  Carla T. Braconi³  M. Jimena Afonso⁴  Karina A. Gomez⁵  Paula M. Berguer⁶  Ariadna Soto⁶  Sabrina E. Vinzón⁷  Felipe J. Núñez⁷  Osvaldo L. Podhajcer⁷  Gregorio D. Ríos⁷  Eduardo G. A. Cafferata⁷  M. Verónica López⁷  Andrea S. Llera⁷  Diana Aguilar-Cortes⁷  Maximiliano Sanchez-Lamas⁸ 

[1] Centro de Medicina Comparada (ICiVet-Litoral), Universidad Nacional del Litoral—CONICET, Santa Fe S3080HOF, Argentina;Discipline of Gynecology, Department of Medicine, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Pablo 04021-001, Brazil;Discipline of Microbiology, Department of Microbiology, Immunology and Parasitology—DMIP, Paulista School of Medicine, Federal University of São Paulo—UNIFESP, Sao Pablo 04021-001, Brazil;Fundación Instituto Leloir, Buenos Aires C1405BWE, Argentina;Laboratorio de Biología e Inmunología de las Infecciones por Tripanosomátidos, Instituto de Investigaciones en Ingeniería Genética y Biología Molecular Dr. Héctor N. Torres (CONICET), Buenos Aires C1428ADN, Argentina;Laboratory of Immunology and Molecular Microbiology, Fundación Instituto Leloir—CONICET (IIBBA), Buenos Aires C1405BWE, Argentina;Laboratory of Molecular and Cellular Therapy, Fundación Instituto Leloir—CONICET (IIBBA), Buenos Aires C1405BWE, Argentina;Securitas Biosciences, Montevideo 11100, Uruguay;

关键词: COVID vaccine;    hybrid adenovirus vector;    immune response;    variants of concern;   

DOI  :  10.3390/vaccines9101106

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown