PHASE-SEPARATING MICROBUBBLES FUNCTIONING AS VACCINE DEPOTS

Abstract

Failure in receiving a booster for specific vaccines contributes to incomplete seroconversion, particularly in the developing world. Single injection vaccine technology could potentially be a solution such that health care personnel would not need to meet patients multiple times at designated points in time thereafter. The main challenge for single injection vaccine systems to date is controlling the stability of the antigen. to maintain the antigenic protein structure while in the physiological environment. We engineered a novel phase-separating microbubble technology which could function as an injectable depot which we hypothesize will enable us to control the microenvironment of the antigen for the durations required, in addition to controlling the antigen release time.

We have successfully accomplished the following Main Specific Aims and subaims: Main Specific Aim 1: Synthesize polymers for microbubbles formation and Engineer methods for stabilizing Microbubbles: 1A: Synthesize PCL and PLGA library at different molecular weights and characterizing the polymers 1B: Synthesize acrylate polymers for microbubbles 1C: Engineer stable microbubble through UV cure and lyophilization 1D: Engineering the microbubbles to be stationary for maintaining sphere shape during the curing process and the inject of the cargo 1E: Engineering the cargo to be stationary within the polymeric microbubble to maximize the release time 1F: Quantify the diameter of the microbubble by varying syringe pump rate and comparing diameter pre- and post-lyophilization 1G: Quantify the angle of the micromotor for injecting cargo into the center of the microbubbles 1H: Engineer a self-contained lyophilization-capable system for the microbubbles Main Specific Aim 2: Engineering cargo release time of the microbubbles: 2A: Quantify how different molecular weights of PCL affect release time of the microbubbles 2C: Quantify how varying the microbubbles’ thickness of the shell controls the release time Main Specific Aim 3: Quantify stability of HIV and Hepatitis B antigens: 3A: Quantify how the HIV gp120/41 and HBsAg ayw antigens are stable in time in an aqueous environment versus in a cryo-protectant context at varying temperatures Our novel phase-separating technology which can form microbubble vaccine depots is a promising method to alleviate stability issues which hinders the single injection vaccine field. Enhancement of antigen stability in the microbubbles will be determined in future work.