Enhancing Vaccine Thermostability with Natural Deep Eutectic Solvents

PROJECT SUMMARY The poor thermostability of vaccines is the most notable factor for their inequitable global distribution. The cold chain system imposes a substantial barrier for equitable global access to safe and potent vaccines. To eliminate or improve this vaccine coverage gap, minimizing the costly and labor-intensive cold chain process is a critical need, which would potentially lead to a major reduction of vaccine wastage. We intend to develop tools for cost- effective ambient temperature storage of vaccines without requiring refrigeration or complicated sample recovery protocols for extended durations. This work will introduce the possibility of improving global vaccine access via offering an innovative approach capable of reducing the costs of vaccine storage and deployment, thereby over- coming vaccine shortage and equity issues. We aim to develop new natural deep eutectic solvents (NatDESs), highly polar and molecularly-tunable or- ganic materials with generally recognized as safe (GRAS) toxicity profiles to improve the thermostability of two important proven vaccine platforms: 1) yellow fever virus as a lipid enveloped, positive sense RNA virus; 2) adenovirus as protein capsid, double stranded DNA virus. The proposed formulations will offer a well-suited platform on which the properties can be readily altered by the selection of ions, enabling the tunable design of media for the long-term stabilization of these vaccine platforms. We expect that the solutions of proposed NatDESs with up to 20 wt% water will prevent hydrolytic and enzymatic degradation of viral genomes and protein capsids, promoting high levels of protection for the viral models. In Aim 1, we will develop a diverse series of novel NatDESs through systematic variations of quaternary ammonium cations, biocompatible anions, and bio-sourced sugars and polyols. To gain in-depth understanding of binding characteristics and molecular mechanisms of interactions in viral samples, we will conduct empirical structure-property-function relationship studies using a combination of simulation and X-ray crystallographic methods. In Aim 2, we will examine their utility for stabilizing viral samples via evaluating their structural integrity, thermostability, and shelf-life by monitoring changes in viral secondary structure, thermal denaturation, and par- ticle morphology. This approach has great potential to resolve the cold chain problem and in turn positively impact global health, coverage and equity, and economic cost, compared to the current technologies. This application will address the key objectives of the AREA (R15) grant mechanism through supporting meritorious research, exposing undergraduate students to research, and strengthening the research environ- ment of two primarily undergraduate institutions. These activities include instruction and the mentoring of women, first-generation, and underrepresented minority students. Summery