Virosomes as an Antigen Delivery System

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Abstract
Live, replicating, vaccines have the advantage that they closely mimick the actual infection and therefore induce a broad and physiologically relevant immune response, involving both a humoral immune response (antibody production) and cell-mediated immunity (cytotoxic T lymphocytes). However, there is an increasing concern about the adverse side effects that may occur as a result of vaccination with replicating pathogen preparations. Therefore, in general killed whole pathogens or (recombinant) subunit vaccines are used for vaccination. These preparations induce satisfying antibody responses although less efficient than live, replicating, vaccines. This is due to the way in which the antigens are processed and presented to the immune system. The development of antigen delivery systems to introduce nonreplicating antigens into presentation pathways that result in activation of the humoral arm of the immune response, but also the cytotoxic T-cell arm is therefore of major interest. Virosomes represent such a unique system for presentation of antigens to the immune system. First, virosomes closely resemble the envelope of the virus they are derived from and therefore constitute an antigen-presentation form superior to isolated surface antigens. In addition, properly assembled virosomes retain the membrane fusion activity of the native virus and, therefore, virosomes may be used to deliver encapsulated, unrelated, antigens to the cytosol of antigen-presenting cells. In this respect, virosomes differ from conventional liposomes which will target enclosed antigens primarily to the phagolysosomal system of macrophages. We have recently exploited both aspects of virosomes, derived from influenza virus, to induce CTL activity against a virosome-encapsulated antigenic peptide and whole protein. Here we will present a short overview of our own investigations on virosomes followed by a number of conclusions and perspectives on the poten tial application of virosomes in new-generation vaccines.