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Development and characterization of influenza M2 ectodomain and/or HA stalk-based DC-targeting vaccines for different influenza infections

Authors :
Gary P. Kobinger
Zhujun Ao
Hiva Azizi
Xiaojian Yao
Darwyn Kobasa
Titus Abiola Olukitibi
Kevin M. Coombs
Mona Mahmoudi
Publication Year :
2021
Publisher :
Cold Spring Harbor Laboratory, 2021.

Abstract

A universal influenza vaccine is required for broad protection against influenza infection. Here, we revealed the efficacy of novel influenza vaccine candidates based on Ebola glycoprotein (EboGP) DC-targeting domain (EΔM) fusion protein technology. We fused influenza hemagglutinin stalk (HAcs) and extracellular matrix protein (M2e) or four copies of M2e (referred to as tetra M2e (tM2e)) with EΔM to generate EΔM-HM2e or EΔM-tM2e, respectively, and revealed that EΔM facilitates DC/macrophage targeting in vitro. In a mouse study, EΔM-HM2e- or EΔM-tM2e-pseudotyped viral particles (PVPs) induced significantly higher titers of anti-HA and/or anti-M2e antibodies. We also developed recombinant vesicular stomatitis virus (rVSV)-EΔM-HM2e and rVSV-EΔM-tM2e vaccines that resulted in rapid and potent induction of HA and/or M2 antibodies in mouse sera and mucosa. Importantly, vaccination protects mice from influenza H1N1 and H3N2 challenges. Taken together, our study suggests that recombinant rVSV-EΔM-HM2e and rVSV-EΔM-tM2e are efficacious and protective universal vaccines against influenza.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........eb0b815159f05feab02fe67230926317
Full Text :
https://doi.org/10.1101/2021.10.07.463539