Sublingual Supramolecular Vaccines and Immunotherapies

Lineage-directed or other multi-dose strategies involving the sequential delivery of antigens across weeks or months are receiving increasing scientific interest towards a range of diseases currently lacking vaccines. However, repeated dosing of vaccines over extended time frames presents challenges, including thermal sensitivity of current vaccines and the necessity for many visits to healthcare providers, which is burdensome on the US Healthcare system. This project seeks to utilize supramolecular peptide biomaterial vaccines engineered specifically for the sublingual route to provide for effective vaccination in a manner that is shelf-stable and self-administrable. The project aims to design a shelf-stable, easily administered, and minimally reactogenic vaccine platform as an alternative to needle-based vaccines relying on continuous refrigeration. We will build upon the innovative self-assembling peptide platforms recently introduced by our group and others in order to elucidate factors necessary for maximizing and adjusting sublingual vaccination responses. In preliminary work, we have established the proof-of-concept of a tablet-based supramolecular vaccination technology, Supramolecular Immunization with Peptides SubLingually (SIMPL), but the key design parameters for adjusting the strength and quality of immune responses remain to be articulated. Therefore the objective of the project is to articulate these design rules, using multifactorial Design-of-Experiments (DOE) approaches to ascertain how supramolecular size, charge, mucoadhesivity, and adjuvant complexation influences the lymphatic trafficking and humoral and cellular responses sublingually in mouse models. Critical proofs-of-concept will be established for influenza, zika, and HIV-1. Finally, SIMPL will be established as a basis for multi-dose lineage-directed vaccination in mice and rabbits. Our collaborative team is facilitated by the proximity of the Pratt School of Engineering and the Duke Human Vaccine Institute (DHVI), providing a unique opportunity to combine perspectives from Bioengineers and biomaterials specialists (Collier lab) and immunologists and vaccine specialists (Fouda lab).