Access Type

Open Access Thesis

Date of Award

January 2016

Degree Type

Thesis

Degree Name

M.S.

First Advisor

Haipeng Liu

Abstract

Adjuvants are immunomodulators which enhance immune responses to vaccines. However, parenteral administration of unformulated adjuvants fails to reach lymph nodes (LNs), the anatomic organ where the primary functions of immune cells are orchestrated. The LN-targeting delivery plays the key roles in promoting immune activation and has the great potential to transform disease treatment. The main goal of this thesis is to develop efficient vaccine delivery systems to target therapeutics into draining lymph nodes (dLNs) for ensuring their immunostimulatory activity. We introduced therapeutic applications of activating TLR9 with synthetic CpG oligodeoxynucleotide (ODN) agonists in nanoparticle or molecular form to activate immune responses in animal models. As a nanoparticle deliver platform, positively charged silica nanoparticles (SiNPs) were explored to load immunomodulators that are capable of targeting dLNs and mimicking the size, geometry and surface feathers of live viral pathogens. Immunization with nanoparticles showed potent cellular and humoral immunity superior to vaccination with soluble CpG ODNs.

We next explored the transdermal delivery platform using dissolving microneedle arrays (MNs), which can penetrate the skin and facilitate the rapid release of vaccine components in epidermis. We combined this strategy with an albumin ‘hitchhiking’ approach that can promote interaction with and uptake across the lymphatic endothelium. Vaccination via MNs generated robust immune responses, showing enhanced T cell and antibody responses. We characterized the morphology and vaccine loading capabilities of MNs, and systematically explored how the transdermal delivery of molecular vaccines impacted cellular and humoral immunogenicity. We expect that the results of our work will contribute to the advancement of vaccine delivery systems and will help to develop more efficient therapeutics for treating disease or cancer.

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