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ACS Infect Dis . Synthetic Multicomponent Nanovaccines Based on the Molecular Co-assembly of β-Peptides Protect against Influenza A Virus

tetano

Editor, Senior Moderator
ACS Infect Dis


. 2023 May 18.
doi: 10.1021/acsinfecdis.2c00610. Online ahead of print. Synthetic Multicomponent Nanovaccines Based on the Molecular Co-assembly of β-Peptides Protect against Influenza A Virus

Salma Bricha[SUP] 1 2 3 4 5 [/SUP], Mélanie Côté-Cyr[SUP] 1 3 4 5 [/SUP], Thomas Tremblay[SUP] 3 6 [/SUP], Phuong Trang Nguyen[SUP] 1 3 4 5 [/SUP], Philippe St-Louis[SUP] 2 4 5 [/SUP], Denis Giguère[SUP] 3 6 [/SUP], Denis Archambault[SUP] 2 4 5 [/SUP], Steve Bourgault[SUP] 1 3 4 5 [/SUP]



Affiliations
Abstract

Peptides with the ability to self-assemble into nanoparticles have emerged as an attractive strategy to design antigen delivery platforms for subunit vaccines. While toll-like receptor (TLR) agonists are promising immunostimulants, their use as soluble agents is limited by their rapid clearance and off-target inflammation. Herein, we harnessed molecular co-assembly to prepare multicomponent cross-β-sheet peptide nanofilaments exposing an antigenic epitope derived from the influenza A virus and a TLR agonist. The TLR7 agonist imiquimod and the TLR9 agonist CpG were respectively functionalized on the assemblies by means of an orthogonal pre- or post-assembly conjugation strategy. The nanofilaments were readily uptaken by dendritic cells, and the TLR agonists retained their activity. Multicomponent nanovaccines induced a robust epitope-specific immune response and completely protected immunized mice from a lethal influenza A virus inoculation. This versatile bottom-up approach is promising for the preparation of synthetic vaccines with customized magnitude and polarization of the immune responses.

Keywords: TLR agonists; conjugation; nanofilaments; nanovaccine; peptide self-assembly.

 
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