Influenza virosomes in vaccine development.

Influenza virosomes can be regarded as unilamellar liposomes carrying the spike proteins of influenza virus on their surface. Vaccination with influenza virosomes elicits high titers of influenza-specific antibodies, indicating that HA (and NA) reconstituted into a membranous environment exhibit strong immunogenicity. Moreover, virosomes can be used as presentation systems for unrelated antigens bound to the virosome surface. Because of their intrinsic adjuvant activity, virosomes support antibody formation and induction of T-helper cell responses against such surface-associated antigens. Provided that the fusogenic properties of the reconstituted HA are retained, virosomes can also be used to elicit cytotoxic T-cell responses against encapsulated antigens. Vaccines capable of activating the cellular branch of the immune response can be very important for protection against acute virus infections, especially for viruses with rapidly changing envelope glycoproteins like HIV and influenza virus. Moreover, virosomes can suit as powerful carriers in the development of prophylactic and immunotherapeutic strategies against cancer and premalignant disease. The use of virosomes as commercial influenza vaccine and as commercial adjuvant for a hepatitis A vaccine demonstrates that production of virosomes on an industrial scale is feasible, both technically and economically. The industrial production procedure currently followed has not been designed to retain the functional properties of HA. In fact, several steps in the procedure are probably incompatible with retention of fusion activity. As mentioned previously the fusogenic properties of virosomes are important for CTL activation and might also play a role in the induction of T-helper cell and antibody responses. Therefore, a number of key adaptations in the virosome production protocol will be necessary. Thus improved, virosomes are very attractive devices for the development of highly efficacious vaccines against a range of antigens.