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A Recombinant VSV-Based Bivalent Vaccine Effectively Protects against Both SARS-CoV-2 and Influenza A Virus Infection.
Ao, Zhujun; Ouyang, Maggie J; Olukitibi, Titus A; Warner, Bryce; Vendramelli, Robert; Truong, Thang; Meilleur, Courtney; Zhang, Manli; Kung, Sam; Fowke, Keith R; Kobasa, Darwyn; Yao, Xiaojian.
  • Ao Z; Laboratory of Molecular Human Retrovirology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Ouyang MJ; Department of Medical Microbiology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Olukitibi TA; Laboratory of Molecular Human Retrovirology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Warner B; Department of Medical Microbiology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Vendramelli R; Laboratory of Molecular Human Retrovirology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Truong T; Department of Medical Microbiology, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Meilleur C; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canadagrid.415368.d, Winnipeg, Canada.
  • Zhang M; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canadagrid.415368.d, Winnipeg, Canada.
  • Kung S; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canadagrid.415368.d, Winnipeg, Canada.
  • Fowke KR; Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canadagrid.415368.d, Winnipeg, Canada.
  • Kobasa D; Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
  • Yao X; Department of Immunology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitobagrid.21613.37, Winnipeg, Manitoba, Canada.
J Virol ; 96(18): e0133722, 2022 09 28.
Article in English | MEDLINE | ID: covidwho-2019728
ABSTRACT
COVID-19 and influenza are both highly contagious respiratory diseases that have been serious threats to global public health. It is necessary to develop a bivalent vaccine to control these two infectious diseases simultaneously. In this study, we generated three attenuated replicating recombinant vesicular stomatitis virus (rVSV)-based vaccine candidates against both SARS-CoV-2 and influenza viruses. These rVSV-based vaccines coexpress SARS-CoV-2 Delta spike protein (SP) bearing the C-terminal 17 amino acid (aa) deletion (SPΔC) and I742A point mutation, or the SPΔC with a deletion of S2 domain, or the RBD domain, and a tandem repeat harboring four copies of the highly conserved influenza M2 ectodomain (M2e) that fused with the Ebola glycoprotein DC-targeting/activation domain. Animal immunization studies have shown that these rVSV bivalent vaccines induced efficient humoral and cellular immune responses against both SARS-CoV-2 SP and influenza M2 protein, including high levels of neutralizing antibodies against SARS-CoV-2 Delta and other variant SP-pseudovirus infections. Importantly, immunization of the rVSV bivalent vaccines effectively protected hamsters or mice against the challenges of SARS-CoV-2 Delta variant and lethal H1N1 and H3N2 influenza viruses and significantly reduced respiratory viral loads. Overall, this study provides convincing evidence for the high efficacy of this bivalent vaccine platform to be used and/or easily adapted to produce new vaccines against new or reemerging SARS-CoV-2 variants and influenza A virus infections. IMPORTANCE Given that both COVID-19 and influenza are preferably transmitted through respiratory droplets during the same seasons, it is highly advantageous to develop a bivalent vaccine that could simultaneously protect against both COVID-19 and influenza. In this study, we generated the attenuated replicating recombinant vesicular stomatitis virus (rVSV)-based vaccine candidates that target both spike protein of SARS-Cov-2 Delta variant and the conserved influenza M2 domain. Importantly, these vaccine candidates effectively protected hamsters or mice against the challenges of SARS-CoV-2 Delta variant and lethal H1N1 and H3N2 influenza viruses and significantly reduced respiratory viral loads.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Vaccines, Combined / Influenza, Human / Influenza A Virus, H1N1 Subtype / Vesicular Stomatitis / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01337-22

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Influenza Vaccines / Vaccines, Combined / Influenza, Human / Influenza A Virus, H1N1 Subtype / Vesicular Stomatitis / COVID-19 Type of study: Experimental Studies Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: J Virol Year: 2022 Document Type: Article Affiliation country: Jvi.01337-22