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Vinyl Sulfone-functionalized Acetalated Dextran Microparticles as a Subunit Broadly Acting Influenza Vaccine

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  • Recent Advances in Drug Delivery
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Abstract

Influenza is a global health concern with millions of infections occurring yearly. Seasonal flu vaccines are one way to combat this virus; however, they are poorly protective against influenza as the virus is constantly mutating, particularly at the immunodominant hemagglutinin (HA) head group. A more broadly acting approach involves Computationally Optimized Broadly Reactive Antigen (COBRA). COBRA HA generates a broad immune response that is capable of protecting against mutating strains. Unfortunately, protein-based vaccines are often weekly immunogenic, so to help boost the immune response, we employed the use of acetalated dextran (Ace-DEX) microparticles (MPs) two ways: one to conjugate COBRA HA to the surface and a second to encapsulate cGAMP. To conjugate the COBRA HA to the surface of the Ace-DEX MPs, a poly(L-lactide)-polyethylene glycol co-polymer with a vinyl sulfone terminal group (PLLA-PEG-VS) was used. MPs encapsulating the STING agonist cGAMP were co-delivered with the antigen to form a broadly active influenza vaccine. This vaccine approach was evaluated in vivo with a prime-boost-boost vaccination schedule and illustrated generation of a humoral and cellular response that could protect against a lethal challenge of A/California/07/2009 in BALB/c mice.

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Acknowledgements

Abstract figure and Fig. 1b were in part created with BioRender.com. This work was performed in part at the Chapel Hill Analytical and Nanofabrication Laboratory, CHANL, a member of the North Carolina Research Triangle Nanotechnology Network, RTNN, which is supported by the National Science Foundation, Grant ECCS-2025064, as part of the National Nanotechnology Coordinated Infrastructure, NNCI. We thank Dr. Amar S. Kumbhar of CHANL for his assistance with SEM characterization.

Funding

Funding for this work was supported by National Institutes of Health (NIH) NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) Contract #75N93019C00052 (PI: Ross) and NIH R01AI147497 (PI: Ainslie). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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  1. Cole J. Batty, Liubov M. Lifshits, and Dylan A. Hendy contributed equally.

Authors and Affiliations

  1. Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 4211 Marsico Hall, 125 Mason Farm Road, Chapel Hill, North Carolina, 27599, USA

    Cole J. Batty, Liubov M. Lifshits, Dylan A. Hendy, Meital Eckshtain-Levi, Luis A. Ontiveros-Padilla, Eric M. Bachelder & Kristy M. Ainslie

  2. Florida Research and Innovation Center, Port Saint, Cleveland Clinic Florida, Port St. Lucie, Florida, USA

    Michael A. Carlock & Ted M. Ross

  3. Center for Vaccines and Immunology, University of Georgia, Athens, Georgia, USA

    Ted M. Ross

  4. Department of Infectious Diseases, University of Georgia, Athens, Goergia, USA

    Ted M. Ross

  5. Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    Kristy M. Ainslie

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

    Kristy M. Ainslie

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Contributions

Kristy M. Ainslie (principal investigator) and Eric M. Bachelder (co-principal investigator) designed the experiments and wrote the first draft of manuscript. Cole J. Batty and Liubov M. Lifshits contributed to writing of manuscript, and other co-authors provided minor edits. Cole J. Batty and Liubov M. Lifshits prepared figures for the manuscript. Ted M. Ross (co-principal investigator) provided COBRA HA for the experiments. Michael A. Carlock conducted HAI experiment. Liubov M. Lifshits, Dylan H. Hendy, and Meital Eckshtain-Levi carried out synthesis and characterization of materials. Cole J. Batty, Dylan A. Hendy, and Luis Ontiveros-Padilla carried out in vivo experiments. Dylan H. Hendy revised the manuscript in response to reviewer’s comments.

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Correspondence to Kristy M. Ainslie.

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Batty, C.J., Lifshits, L.M., Hendy, D.A. et al. Vinyl Sulfone-functionalized Acetalated Dextran Microparticles as a Subunit Broadly Acting Influenza Vaccine. AAPS J 25, 22 (2023). https://doi.org/10.1208/s12248-023-00786-6

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