Vaccines for diseases ranging from HIV to cancer will require strategies that provide better control over specific characteristics of immune response. Biomaterials offer great potential in this area owing to their ability to co-deliver signal that can help polarize how immune function. However, many biomaterials – including ubiquitous polymers such as poly(lactide-co-glycolide) – stimulate inflammatory pathways even in the absence of other signals (e.g., adjuvants). While this feature can be harnessed, this intrinsic immunogenicity also hinders rational design because the carrier can alter how other vaccine components are received. We hypothesized that polyelectrolyte multilayers (PEMs) self-assembled entirely from immune signals might simplify vaccine composition while also mimicking attractive features of polymer particles or other biomaterial vaccine carriers. The immune PEMs (iPEMs) are comprised of peptide antigens and nucleic acid toll-like receptor (TLR) agonists as vaccine adjuvants. iPEMs are first assembled on sacrificial templates through electrostatic interactions between polyIC – a double-stranded RNA that activates the TLR3 stimulatory pathway – and antigenic peptides (e.g., SIINFEKL, "SIIN") exhibiting natural cationic charge or modified with cationic amino acid residues (e.g., arginine). Thus, polyIC serves as a potent molecular adjuvant and a polyanionic film component, while peptide serves as a vaccine antigen and cationic component. EDTA is used as a chelator to remove the core, forming “carrier-free” capsules. These capsules do not require mixing, solvents, or polymer carriers typical of materials-based vaccines. iPEMs also juxtapose the immune signals at high density and the size can be tuned across the nano- and micro-scale by varying the pH during core removal. In mice, iPEMs are trafficked to lymph nodes (Panel A), generating potent primary and secondary recall responses amongst CD8+ T cells (Panel B). These responses are specific to the antigens used to build iPEMs and drive a nearly 5-fold increase in potency compared to soluble vaccines. These cells are also functional, providing a significant improvement in survival during tumor challenge with a 1x106 melanoma cells (B16) expressing an exogenous antigen (Panel C).

Rational vaccine design using self-assembled polyionic immune signals

251st National Meeting (2016)

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