RT Journal Article
SR Electronic
T1 Development and Characterization of Recombinant Vesicular Stomatitis Virus (rVSV)-based Bivalent Vaccine Against COVID-19 Delta Variant and Influenza Virus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.12.14.472657
DO 10.1101/2021.12.14.472657
A1 Zhujun Ao
A1 Maggie Jing Ouyang
A1 Titus Abiola Olukitibi
A1 Bryce Warner
A1 Robert Vendramelli
A1 Thang Truong
A1 Manli Zhang
A1 Sam Kung
A1 Keith R Fowke
A1 Darwyn Kobasa
A1 Xiaojian Yao
YR 2021
UL http://biorxiv.org/content/early/2021/12/15/2021.12.14.472657.abstract
AB COVID-19 and influenza are both highly contagious respiratory diseases with a wide range of severe symptoms and cause great disease burdens globally. It has become very urgent and important to develop a bivalent vaccine that is able to target these two infectious diseases simultaneously. In this study, we generated three attenuated replicating recombinant VSV (rVSV) vaccine candidates. These rVSV-based vaccines co-express SARS-CoV-2 Delta variant spike protein (SP) or the receptor binding domain (RBD) and four copies of the highly conserved M2 ectodomain (M2e) of influenza A fused with the Ebola glycoprotein DC-targeting/activation domain. Animal studies have shown that immunization with these bivalent rVSV vaccines induced efficient but variable levels of humoral and cell-mediated immune responses against both SARS-CoV-2 and influenza M2e protein. Significantly, our vaccine candidates induced production of high levels of neutralizing antibodies that protected cells against SARS-CoV-2 Delta and other SP-pseudovirus infections in culture. Furthermore, vaccination with the bivalent VSV vaccine via either intramuscular or intranasal route efficiently protected mice from the lethal challenge of H1N1 and H3N2 influenza viruses and significantly reduced viral load in the lungs. These studies provide convincing evidence for the high efficacy of this bivalent vaccine to prevent influenza replication and initiate robust immune responses against SARS-CoV-2 Delta variants. Further investigation of its efficacy to protect against SARS-CoV-2 Delta variants will provide substantial evidence for new avenues to control two contagious respiratory infections, COVID-19 and influenza.Competing Interest StatementThe authors have declared no competing interest.