Modular complement assemblies as defined active immunotherapies

Statement of Purpose: Induction of a tunable humoral response is essential for the success of a variety of immunotherapies including vaccines against infectious diseases and active immunotherapies against autologous targets. These therapies often require adjuvants to enhance immunogenicity and confer more durable responses, however adjuvants can induce cell-mediated T-helper (TH) responses, that lead to a diminished therapeutic effect1. For example, we recently found that the addition of a CpG adjuvant to active immunotherapies against TNF-mediated inflammation led to a reduced therapeutic effect, thought to be caused by the biasing of the overall TH response towards a TH1 phenotype2. Here, we demonstrate a new tool for immunotherapies that maintains a TH2 phenotype while simultaneously enhancing antibody responses. Using a materials-based approach, we illustrate the tuning of the adjuvancy of peptide nanofiber vaccines by co-assembbling an engineered, supramolecular complement protein, C3d. Utilizing the βtail system, which allows E. coli expressable proteins to be integrated into nanofibers, supramolecular βtail-C3d can be assembled with immunologically active nanomaterials, wherein the exact C3d and epitope content can be precisely specified in order to generate controllable immune responses.