STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant

Matthew D Gallovic; Robert D Junkins; Adam M Sandor; Erik S Pena; Christopher J Sample; Ariel K Mason; Leslee C Arwood; Rebecca A Sahm; Eric M Bachelder; Kristy M Ainslie; Gregory D Sempowski; Jenny P-Y Ting

doi:10.1016/j.jconrel.2022.05.017

STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant

J Control Release. 2022 Jul:347:356-368. doi: 10.1016/j.jconrel.2022.05.017. Epub 2022 May 18.

Affiliations

¹ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
⁴ Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, USA.
⁵ Department of Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Institute for Inflammatory Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Center for Translational Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jenny_ting@med.unc.edu.

Abstract

The current pandemic highlights the need for effective vaccines against respiratory viruses. An ideal vaccine should induce robust and long-lasting responses with high manufacturing scalability. We use an adjuvant comprised of a Stimulator of Interferon Genes (STING) agonist incorporated in a scalable microparticle platform to achieve durable protection against the influenza virus. This formulation overcomes the challenges presented by the cytosolic localization of STING and the hydrophilicity of its agonists. We evaluated a monoaxial formulation of polymeric acetalated dextran microparticles (MPs) to deliver the STING agonist cyclic GMP-AMP (cGAMP) which achieved >10× dose-sparing effects compared to other published work. Efficacy was evaluated in ferrets, a larger animal model of choice for influenza vaccines. cGAMP MPs with recombinant hemagglutinin reduced viral shedding and improved vaccine outcomes compared to a seasonal influenza vaccine. Importantly, sustained protection against a lethal influenza infection was detected a year after a single dose of the vaccine-adjuvant.

Keywords: Acetetlated dextran; Influenza; STING; Vaccine; Viral immunology.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Adjuvants, Immunologic
Animals
Antibodies, Viral
Ferrets
Humans
Influenza Vaccines*
Influenza, Human*
Orthomyxoviridae Infections* / prevention & control
Seasons
Vaccine Efficacy

Substances

Adjuvants, Immunologic
Antibodies, Viral
Influenza Vaccines

STING agonist-containing microparticles improve seasonal influenza vaccine efficacy and durability in ferrets over standard adjuvant

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

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