Dokumentdetails
ID

oai:pubmedcentral.nih.gov:8153...

Autor
Roth, Gillie A. Saouaf, Olivia M. Smith, Anton A. A. Gale, Emily C. Hernández, Marcela Alcántara Idoyaga, Juliana Appel, Eric A.
Langue
en
Editor

American Chemical Society

Kategorie

ACS AuthorChoice

Jahr

2021

Auflistungsdatum

25.09.2023

Schlüsselwörter
hydrogels adjuvant influenza codelivery pnp hemagglutinin
Metrisch

Zusammenfassung

[Image: see text] The sustained release of vaccine cargo has been shown to improve humoral immune responses to challenging pathogens such as influenza.

Extended codelivery of antigen and adjuvant prolongs germinal center reactions, thus improving antibody affinity maturation and the ability to neutralize the target pathogen.

Here, we develop an injectable, physically cross-linked polymer–nanoparticle (PNP) hydrogel system to prolong the local codelivery of hemagglutinin and a toll-like receptor 7/8 agonist (TLR7/8a) adjuvant.

By tethering the TLR7/8a to a NP motif within the hydrogels (TLR7/8a-NP), the dynamic mesh of the PNP hydrogels enables codiffusion of the adjuvant and protein antigen (hemagglutinin), therefore enabling sustained codelivery of these two physicochemically distinct molecules.

We show that subcutaneous delivery of PNP hydrogels carrying hemagglutinin and TLR7/8a-NP in mice improves the magnitude and duration of antibody titers in response to a single injection vaccination compared to clinically used adjuvants.

Furthermore, the PNP gel-based slow delivery of influenza vaccines led to increased breadth of antibody responses against future influenza variants, including a future pandemic variant, compared to clinical adjuvants.

In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of influenza subunit vaccines.

Roth, Gillie A.,Saouaf, Olivia M.,Smith, Anton A. A.,Gale, Emily C.,Hernández, Marcela Alcántara,Idoyaga, Juliana,Appel, Eric A., 2021, Prolonged Codelivery of Hemagglutinin and a TLR7/8 Agonist in a Supramolecular Polymer–Nanoparticle Hydrogel Enhances Potency and Breadth of Influenza Vaccination, American Chemical Society

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