Heterologous Virus-Like-Particles: Recombinant Nanosystems as Versatile Antigen Delivery Devices for Immune Intervention

Biological protein-based entities that form nanostructures ranging from 8 to 50 nm in size represent promising candidates in the development of novel immunotherapeutics against cancer and microbial pathogens. These recombinant nanoparticles usually consist of major coat or core proteins derived from viruses like for instance papillomavirus, polyomavirus, parvovirus or hepatitis B virus that spontaneously assemble into these highly ordered, supramolecular, icosahedral structures. By genetic engineering of permissive sites or cross-linking to surface-exposed subunit domains these nanoparticles successfully serve as carrier matrix with per se adjuvant activity for the delivery of appropriate guest peptides, protein fragments and complete proteins. Using this nanobiotechnology, potent humoral and cell-mediated immunity with emphasis on CD4 and CD8 T cell responses are induced against self or non-self foreign antigens representing appropriate immunostimulatory epitopes or complete proteins of microbial pathogens or tumor-associated antigens. Breaking of T and B cell tolerance required for therapeutic interventions against cancer represents the hallmark of such an outstanding antigen delivery system. In combination with the increasing identification of validated target antigens from pathogens or tumors, and promising progress in bioprocess development, such nanostructures offer novel homologous or heterologous treatment and prevention opportunities against a variety of malignant and infectious diseases.