The virosome concept for influenza vaccines.

There is a need for more efficacious inactivated influenza vaccines, since current formulations show suboptimal immunogenicity in at-risk populations, like the elderly. More effective vaccines are also urgently needed for an improved influenza pandemic preparedness. In this context, there is considerable interest in virosomes. Virosomes are virus-like particles, consisting of reconstituted influenza virus envelopes, lacking the genetic material of the native virus. Virosomes are produced from influenza virus through a detergent solubilization and removal procedure. Properly reconstituted virosomes retain the cell binding and membrane fusion properties of the native virus, mediated by the viral envelope glycoprotein haemagglutinin. These functional characteristics of virosomes form the basis for their enhanced immunogenicity. First, the repetitive arrangement of haemagglutinin molecules on the virosomal surface mediates a cooperative interaction of the antigen with Ig receptors on B lymphocytes, stimulating strong antibody responses. In addition, virosomes interact efficiently with antigen-presenting cells, such as dendritic cells, resulting in activation of T lymphocytes. In a murine model system, virosomes, as compared to conventional subunit vaccine, which consists of isolated influenza envelope glycoproteins, induce a more balanced T helper 1 versus T helper 2 response, virosomes in particular eliciting stronger T helper 1 responses than subunit vaccine. Also, as a result of fusion of the virosomes with the endosomal membrane, part of the virosomal antigen gains access to the major histocompatibility class I presentation pathway, thus priming cytotoxic T lymphocyte activity. Finally, virosomes represent an excellent platform for inclusion of lipophilic adjuvants for further stimulation of vaccine immunogenicity. By virtue of these characteristics, virosomes represent a promising novel class of inactivated influenza vaccines, which not only induce high virus-neutralizing antibody titres, but also prime the cellular arm of the immune system.