Cobra Hemagglutinin and cGAMP Loaded Ace‐Dex Microparticles Provide a Broadly Active and Shelf‐Stable Influenza Vaccine Platform

Author:

Hendy Dylan A.1ORCID,Pena Erik S.2,Batty Cole J.1ORCID,Ontiveros‐Padilla Luis1ORCID,III John A. Roque1ORCID,Dixon Timothy A.1,Middleton Denzel D.1ORCID,Carlock Michael A.3ORCID,Ross Ted M.345ORCID,Bachelder Eric M.1ORCID,Ainslie Kristy M.126ORCID

Affiliation:

1. Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill 27599 USA

2. Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University USA

3. Florida Research and Innovation Center Port Saint Cleveland Clinic Florida Port St. Lucie FL USA

4. Center for Vaccines and Immunology University of Georgia Athens GA USA

5. Department of Infectious Diseases University of Georgia Athens GA USA

6. Department of Microbiology and Immunology UNC School of Medicine University of North Carolina Chapel Hill NC USA

Abstract

AbstractCurrent FDA‐approved influenza vaccines are limited by variable year to year efficacy, low immunogenicity, and poor stability outside of cold‐chain storage. Polymeric microparticles can overcome many of these issues to provide an improved influenza vaccine platform. Here, an acetalated dextran microparticle platform is used to encapsulate a broadly active influenza COBRA immunogen and the adjuvant cGAMP. Microparticles are fabricated via the highly scalable electrospray method. Mice vaccinated with acetalated dextran microparticles loaded with COBRA and cGAMP produced antibodies with the ability to neutralize antigenically distinct influenza viruses. The microparticles also induced a potent cellular response against the COBRA immunogen. Finally, after storage for 3 months at 40 °C or 6 months at 24 °C, the microparticles produced as strong of an immune response as microparticles stored at −20 °C for the same amount of time. Overall, acetalated dextran microparticles provide a promising platform for a broadly active influenza vaccine.

Funder

National Institutes of Health

Publisher

Wiley

Subject

Pharmacology (medical),Biochemistry (medical),Genetics (clinical),Pharmaceutical Science,Pharmacology,Medicine (miscellaneous)

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