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Published on: October 20, 2020
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Optimizing delivery in a multivalent subunit influenza vaccine using mixed polymeric microparticle degradation rates
Erik S Pena1, Luis Ontiveros-Padilla2, Nicole R Lukesh2
1Department of Biomedical Engineering, North Carolina State University and University of North Carolina, Chapel Hill, NC, USA.
Summary
This study developed a novel multivalent influenza vaccine using acetalated dextran microparticles (Ace-DEX MPs) that encapsulate antigens and adjuvants. Optimizing microparticle degradation rates enhanced immune responses and provided broad protection against influenza strains.
Area of Science:
- Vaccinology
- Immunology
- Materials Science
Background:
- Seasonal influenza vaccines have variable efficacy, and novel strains like H5N1 pose significant threats.
- Broadly acting vaccines require adjuvants and advanced delivery systems for enhanced immunogenicity, dose sparing, and thermostability.
- Acetalated dextran microparticles (Ace-DEX MPs) are explored as a delivery platform for improved vaccine performance.
Purpose of the Study:
- To investigate acetalated dextran microparticles (Ace-DEX MPs) encapsulating cGAMP (adjuvant) and computational optimized broadly reactive antigen (COBRA) hemagglutinin (HA) for a multivalent influenza vaccine.
- To evaluate the impact of mixing Ace-DEX MPs with different degradation rates on the immune response.
- To assess the protective efficacy of the developed vaccine against influenza strains in animal models.
Main Methods:
- Formulation of Ace-DEX MPs encapsulating cGAMP and COBRA HA proteins.
- Vaccination of mice with Ace-DEX MPs with varying degradation kinetics (fast, slow, or mixed).
- Assessment of immune responses (IgG2a titers, cytokine production) in mice and protection studies in ferrets against influenza challenge.
Main Results:
- Slower-degrading cGAMP MPs induced higher IgG2a titers and IL-2 production.
- A mix of fast and slow-degrading cGAMP MPs maximized IFN-γ production in mice.
- A trivalent COBRA formulation with slow-degrading cGAMP MPs conferred protection in ferrets against H1, H3, and H5 strains.
- Co-delivery of antigens with differential degradation rates reduced single antigen dominance.
Conclusions:
- Ace-DEX MPs are a versatile platform for developing effective multivalent influenza vaccines.
- Microparticle degradation kinetics significantly influence the type and magnitude of the immune response.
- This approach offers potential for improved vaccine efficacy, dose sparing, and thermostability against diverse influenza strains.
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