Virosomes influenza vaccines

Herzog C, Metcalfe IC, Schaad UB (2002) Virosome influenza vaccine in children. Vaccine 20(Suppl 5) B24-B28... 

Virosomes are liposomes containing viral fusion proteins that allow efficient entering into cells fusion with endosome membranes. Viral fusion proteins become activated in the low pH environment in the endosome to release its contents into the cytosol. Hepatitis A and influenza vaccines constructed on virosomes elicited fewer local adverse reactions than did their classic counterparts and displayed enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic when administered by the intranasal route. Other studies have suggested that immunopotentiating reconstituted influenza virosomes can be a suitable delivery system for synthetic... 

The current status of adjuvanted influenza vaccines has been reviewed (26). The authors concluded that the vaccine produces a higher titer of antibodies than non-adjuvanted or virosomal vaccines. Local reactions occur more often, but are mild and transient. The results of a trial with two doses of an intranasally administered inactivated virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant in 106 volunteers aged 33-63 years have been reported (27). About 50% of vaccinees had local adverse reactions (44% after the first dose and 54% after the second dose) or systemic adverse reactions (48 and 46%) after administration of the vaccine. Rhinorrhea, sneezing, and headache were the most common reactions they were mild and transient and resolved within 24-48 hours. No febrile reactions were associated with immunization. Between 77 and 92% of vaccinees developed protective hemagglutination inhibition antibody titers against the two influenzae A strains of the vaccine, whereas protective antibody titers against the B strain of the vaccine were achieved in only 49-58%. 

Gluck R, Mischler R, Durrer P, Furer E, Lang AB, Herzog C, Cryz SJ Jr. Safety and immunogenicity of intranasally administered inactivated trivalent virosome-formulated influenza vaccine containing Escherichia coli heat-labile toxin as a mucosal adjuvant J Infect Dis 2000 181(3) 1129-32. 

Huckriede A, Bungener L, Daemen T, Wilschut J (2003) Influenza virosomes in vaccine development. Meth Enzymol 373 74-91... 

During the 1990s, a virosomal hepatitis A vaccine and in 2001, an influenza vaccine were developed by Berna Biotech by applying the virosome technology. 

Virosomes are liposomal carriers for antigens consisting of unilamellar vesicles with a mean diameter of 150 nm (approximately the size of a real virus) they are now commercially available for hepatitis and influenza vaccination. ... 

Immunopotentiating reconstituted influenza virosomes (IRTV) are spherical 150-nm sized particles consisting of a phospholipid bilayer in which influenza virus A/Singapore strain-derived hemagglutinin (HA) and neuraminidase (NA) are intercalated. As such, they resemble and mimic the influenza virus envelope. The difference from conventional liposome formulations lies in the inclusion of the viral envelope proteins HA and NA as well as viral phospholipids. Especially, the inclusion of influenza virus HA provides IRIV with delivery and immimogenic capacities. IRTV are licensed for human use as adjuvant in hepatitis A vaccination and as influenza subunit vaccine (1). 

Schumacher R, Adamina A, Zurbriggen R, et al. Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation. Vaccine 2004 22 714. 

Poltl-Frank, F. Zurbriggen, R. Helg, A. Stuart, F. Robinson, J. Gluck, R. Pluschke, G. Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide-based vaccine. Clin. Exp. Immunol. 1999, 117, 496-503. 

To increase immunogenicity, the hepatitis A vaccines commercially available are coupled to adjuvant aluminium phosphate or aluminium hydroxide. However, alum precipitates provoke inflammatory responses at the injection site. Immunostimulating reconstituted influenza virosomes have therefore been used as an alternative adjuvant. In 1994, a hepatitis A vaccine using the new adjuvant was licensed in Switzerland, and it was later approved for use in other countries the vaccine was well tolerated and highly immunogenic (SEDA-20,290) (SEDA-22,344). Nine people with a history of ocular sensitivity were immunized with hepatitis B, without untoward reactions. However, this result in such a small series should not be overestimated (75). There have been reports of three cases of inflammatory nodular reactions after hepatitis B immunization aluminium allergy was confirmed (76-78). 

Two commercial vaccines based on virosome technology are currendy on the market. Epaxal (Berna Biotech Ltd, Bern, Switzerland), a hepatitis A vaccine, has inactivated hepatitis A virus particles adsorbed on the surface of the immunopotentiating reconstituted influenza virosomes (IRIV). In Inflexal V (Berna Biotech Ltd) the virosome components themselves are the vaccine protective antigens (185). Recently, in phase I study liposome-encapsulated malaria vaccine (containing monophosphoryl lipid A as adjuvant in the bilayer), the formulation showed induction of higher level of anti-malaria antibody in human volunteers (186). Some liposomal formulations are under investigation in preclinical studies against Yersina pestis, ricin toxin and Ebola Zaire virus (77, 187). 

Cusi MG et al (2004) Efficient delivery of DNA to dendritic cells mediated by influenza virosomes. Vaccine 22 735-739... 

Ruf BR, Colberg K, Frick M, Preusche A (2004) Open, randomized study to compare the immunogenicity and reactogenicity of an influenza split vaccine with an MF59-adjuvanted subunit vaccine and a virosome-based subunit vaccine in elderly. Infection 32 191-198... 

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