Initiating an immune response requires specialized antigen presenting cells (APCs) to present foreign antigens with co-stimulatory molecules. Toll-like receptors (TLRs) are often involved in expression of co-stimulatory molecules. TLRs detect patterns common in viruses and bacteria, but not humans. Both the location and frequency of TLR agonist (TLRa) detection help define the type of immune response generated. Simple platforms allowing control over how and where immune signals are processed would improve rational vaccine design. Using electrostatic interactions, we synthesized immune polyelectrolyte multilayers (iPEMs) composed entirely of anionic TLRa and cationic peptide antigen. This approach confers advantages of biomaterials (e.g. co-delivery) without carrier components. This simplicity allows isolation and quantification of synergies achieved by packaging immune signals into particles. We hypothesized co-delivery of TLRa and antigen in iPEMs would enhance immunogenicity over soluble delivery. iPEMs were incubated with primary APCs to study particle-cell interactions over time. iPEM treatment promoted co-internalization of both antigen and TLRa (A) through caveolae-mediated endocytosis (B). Uptake of iPEMs by APCs began in minutes (C), and drove faster downstream processing and APC activation relative to dose-matched free TLRa (D). Our findings provide insight into specific mechanisms by which particulate vaccines enhance initiation of immune response; insight that can be used to design vaccines with precise control over immune response.

Deciphering uptake and trafficking of nanostructured materials built from immune signals

2019 Spring National Meeting

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