Degree Type

Dissertation

Date of Award

2014

Degree Name

Doctor of Philosophy

Department

Chemical and Biological Engineering

Major

Chemical Engineering

First Advisor

Surya Mallapragada

Abstract

The main objective of this project is the development of a safe and effective vaccine against respiratory pathogens including the highly pathogenic avian influenza (HPAI) H5N1. Amphiphilic pentablock copolymers based on Pluronic F127 and poly(2-diethylaminoethyl methacrylate (PDEAEM) have several characteristics that make them promising candidates as injectable vaccine carriers and adjuvants. Individual block copolymer molecules self-assemble into micelles in aqueous solutions. These micelles can be used to encapsulate protein for vaccine delivery. As the concentration of the block copolymer increases, the micelles form a temperature dependent gel and the length of the PDEAEM blocks control the dissolution rate of the gels. An injectable formulation can be designed to gel at physiological temperatures and form an antigenic depot. In addition, these biocompatible pentablock copolymers are based on pluronic, which is FDA approved as an injectable material. In order to design an efficacious next-generation vaccine against HPAI H5N1 several specific research goals were laid out including: (1) Design, synthesis, and optimization of the pentablock copolymer vaccine platform; (2) Evaluation of vaccine efficacy in vitro and in vivo; and (3) Immunization of mice with the pentablock copolymer vaccine to asses an immune response. Our block copolymer injectable delivery platform demonstrates the ability to sustain the release of antigen with minimal effects on protein stability or antigenicity and persist at the injection site. We have also successfully modified the polymers through an azide-alkyne click reaction to include mannose moieties that act as ligands for pattern recognition receptors on antigen presenting cells. These data coupled with the strong immune response demonstrate the potential for block copolymers for use simultaneously for injectable delivery and as a vaccine adjuvant platform.

DOI

https://doi.org/10.31274/etd-180810-5490

Copyright Owner

Justin Adams

Language

en

File Format

application/pdf

File Size

177 pages

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