POLYMERIC PRINT HYDROGEL NANOPARTICLES AS A DELIVERY PLATFORM FOR SUBUNIT VACCINE ANTIGENS AND ADJUVANTS

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  • March 19, 2019
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  • Mueller, Sarah
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Vaccines consisting of purified soluble antigens rather than killed or attenuated whole pathogens have shown great promise in increasing vaccine safety. However, these subunit vaccines (proteins, DNA, polysaccharides, lipids) are susceptible to degradation and are usually less immunogenic than whole pathogen vaccines. Subunit vaccines have shown increased efficacy when delivered in particulate form compared to soluble form. Previous research, however, has been limited by particle fabrication methods that are often incapable of yielding homogeneous particles and are incompatible with industrial scale-up. The use of Particle Replication in Non-wetting Templates (PRINT®) technology avoids these issues, allowing for precise control over particle size, shape, composition, and surface characteristics. In addition, PRINT is a highly scalable, GMP compliant process. Herein, PRINT is employed to fabricate polymeric hydrogel nanoparticles for the delivery of novel pro-adjuvants and protein antigens in vitro and in vivo. The model protein antigen, ovalbumin (OVA), was directly conjugated to the surface of nanoparticles through a poly(ethylene glycol) (PEG) linker. Surface presentation of OVA led to antigen processing and presentation by antigen presenting cells and elicited robust immune responses. The linker chemistries utilized for this model antigen are applicable to a range of clinically relevant vaccine antigens, with studies toward a dengue virus vaccine and an influenza vaccine in preliminary phases. Resiquimod, a toll-like receptor 7/8 agonist and vaccine adjuvant, was used to synthesize a polymerizable, acid-labile pro-adjuvant. The pro-adjuvant loaded nanoparticles were capable of steadily releasing the original, active adjuvant when exposed to endosomal pH (pH 5), while protecting the adjuvant from premature release at physiological pH (pH 7.4). This allowed for intracellular delivery of resiquimod and limited systemic exposure. Therefore, PRINT nanoparticles can be formulated into potent particulate vaccines for controlled and efficiently co-delivery of adjuvants and antigens. Overall, these efforts may lead to new and efficacious vaccines to a wide variety of infectious diseases.
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  • In Copyright
Advisor
  • Kabanov, Alexander
  • You, Wei
  • DeSimone, Joseph M.
  • Sheiko, Sergei
  • Ting, Jenny P.-Y.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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  • This item is restricted from public view for 1 year after publication.
Date uploaded
  • April 23, 2015

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