(648g) Invited Talk: Rational Design of Nanovaccines and Nanomedicines Using Data Analytics and High Throughput Screening

The design of vaccines to address infectious diseases is fraught with challenges, including poor immunogenicity, cold storage needs, multiple dose requirements, and needle-based delivery methods that require medical professionals to administer. We have developed a cross-disciplinary approach at the intersection of polymer chemistry, nanotechnology, and immunology for the molecular design of a safe, needle-free, and efficacious nanoparticle-based vaccine (i.e., nanovaccine) platform technology that can address these challenges. We have used a bottom-up approach to design nanovaccine formulations based on biodegradable amphiphilic polyanhydride nanoparticles, small molecule adjuvants, and vaccine antigens, capable of mimicking a natural infection and inducing a robust immune response with long-lived protection. However, the large parameter space of nanoparticle and adjuvant chemistries and antigens makes rational design of vaccine formulations daunting.

Similarly, polymer-based nanomedicines can improve the functional efficacy of existing therapies by improving drug biodistribution and targeting. While first principles models are valuable in understanding the physical phenomena during drug transport, the significant diversity in polymer and drug systems results in large numbers of combinations of (and interactions between) polymer, drug, and nanoparticle properties with nonlinear behavioral relationships and a large data space. These factors complicate both first-principles modeling and rational design of nanomedicine formulations.

In this talk, we describe two examples where cellular and immunological phenomena induced by appropriate combinations of nanoparticles, adjuvants, and antigens/drugs were achieved by integrating multiscale experiments, data analytics, and high-throughput screening approaches. The first example focuses on the rational design of “just right” influenza nanovaccines that induce protective immunity in aged subjects. In this work, we showed using a combination of immunological experiments and statistical models that “just right” nanovaccine formulations that balance the induction of robust immune responses with inflammation provide protective immunity in aged subjects, setting the state for rational design of vaccines for older adults. The second example focuses on a hybrid informatics approach to identify polymer, antibiotic, and particle determinants of nanomedicine activity against multi-drug resistant bacteria, and to model nanomedicine performance. Graph analysis provided dimensionality reduction while preserving nonlinear descriptor-property relationships, enabling accurate modeling of nanomedicine performance. This data analytics-guided approach provides an important step toward the development of a rational design framework for antimicrobial nanomedicines against resistant infections by selecting appropriate carriers and payloads for improved potency.

Overall, this rational approach for designing and tailoring novel amphiphilic materials as nanoscale adjuvants and nanomedicines has the tantalizing potential to catalyze the rapid development of next generation countermeasures against emerging and re-emerging diseases.