Submission ID 91899

Poster Code HR-P-71
Title of Abstract A Novel M2e-based DC-Targeting Influenza Universal Vaccine
Abstract Submission Introduction: The continuous emergence of the influenza virus results in over 650,000 deaths annually despite the annual vaccination, thus, calling for a novel universal influenza vaccine. Interestingly using Ebola glycoprotein (EboGP) to target dendritic cells (DCs) is highly immunogenic. We, therefore, developed novel DC-targeting influenza antigens by fusing the EboGP DC-targeting domain (EΔM) to conserved influenza hemagglutinin stalk regions and the ectodomain of matrix protein (M2e) (HM2e) generating EΔM-HM2e or four copies of M2e (tM2e) generating EΔM-tM2e. Likewise, the co-infection of influenza and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 remains overwhelming. We also developed influenza and SARS-CoV-2 bivalent vaccines. Methods: In this study, the EΔM-HM2e or EΔM-tM2e was incorporated into virus-like particles (VLPs), and recombinant vesicular stomatitis virus (rVSV) for DC-targeting ability, and antigenicity investigations against influenza respectively. The rVSV-EΔM-tM2e was then incorporated with the SARS-CoV-2 spike protein (SP) (having C-terminal deleted and I742A point mutation) (EM2e/SPΔC1), SP (having S2 deleted) (EM2e/SPΔC2) or the receptor binding domain (EM2e/RBD). We then characterized their immunogenicity property against influenza or SARS-CoV-2 infection in mice or hamsters. Results: Our results revealed that VLP-EΔM-HM2e or EΔM-tM2e could target DCs/macrophages in vitro. Furthermore, rVSV-EΔM-tM2e or EΔM-HM2e intranasally or intramuscularly immunized mice had significantly high levels of induced immune responses and had 100% protection against the H3N2, and 60% or 100% protection against H1N1 respectively. Our Antibody-Dependent Cellular Cytotoxicity assay revealed that the survival rate is antibody-dependent. Furthermore, the EΔM-tM2e in the bivalent vaccines induced robust immune responses and protected against H1N1 in mice with reduced viral loads. While these vaccine candidates also protected against SARS-CoV-2 infection in ferrets. Conclusion: Using our novel strategy, we developed a universal influenza vaccine by fusing influenza-conserved epitopes with EΔM to induce a broader immune response against influenza infections. While the EΔM-tM2e bivalent vaccines also protected against influenza and SARS-CoV-2.
Please indicate who nominated you University of Manitoba
What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? Infection and Immunity
What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? Biomedical
PDF of abstract Titus Olukitibi_ ICAMS Abstract.pdf
2023-01-27 at 15:22:53
Presenter and Author(s) Titus Olukitibi
Titus Olukitibi
Zhujun Ao
Hiva Azizi
Maggi Ouyang
Kevin Coombs
Darwyn Kobasa
Gary Kobinger
Xiaojian Yao

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