Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses

Walid M. Abdelwahab
* ,
Sarah Auclair
,
Timothy Borgogna
,
Karthik Siram
ORCID logo ,
Alexander Riffey
,
Hélène G. Bazin
,
Howard B. Cottam
,
Tomoko Hayashi
,
Jay T. Evans
ORCID logo ,
David J. Burkhart
*
Version 1 : Received: 11 December 2023 / Approved: 12 December 2023 / Online: 12 December 2023 (05:25:44 CET)

A peer-reviewed article of this Preprint also exists.

Abdelwahab, W.M.; Auclair, S.; Borgogna, T.; Siram, K.; Riffey, A.; Bazin, H.G.; Cottam, H.B.; Hayashi, T.; Evans, J.T.; Burkhart, D.J. Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses. Pharmaceutics 2024, 16, 107. Abdelwahab, W.M.; Auclair, S.; Borgogna, T.; Siram, K.; Riffey, A.; Bazin, H.G.; Cottam, H.B.; Hayashi, T.; Evans, J.T.; Burkhart, D.J. Co-Delivery of a Novel Lipidated TLR7/8 Agonist and Hemagglutinin-Based Influenza Antigen Using Silica Nanoparticles Promotes Enhanced Immune Responses. Pharmaceutics 2024, 16, 107.

Abstract

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed > 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Keywords

co-delivery; silica nanoparticles; vaccine adjuvant; toll-like receptor 7/8 (TLR7/8) ligand; INI-4001; influenza virus; hemagglutinin H7

Subject

Medicine and Pharmacology, Immunology and Allergy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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