Biophysical validation of Epaxal Berna, a hepatitis A vaccine adjuvanted with immunopotentiating reconstituted influenza virosomes (IRIV).
Inactivated vaccines usually contain an adjuvant which potentiates the immune response to the antigen. During the last 70 years aluminium salts have been the only adjuvant licensed for human use. The adjuvanting activity is based on their serving as an antigen depot and inducing a localized inflammatory response. Our efforts to develop a potent and well tolerated adjuvant has focussed on the use of immunopotentiating reconstituted influenza virosomes (IRIV). The IRIV base is a liposome with a mean diameter of 150 nm, comprising phosphatidylcholine (PC) and phosphatidylethanolamine (PE). These mammalian phospholipids are virtually non-immunogenic and have enjoyed a long history of use in human pharmaceutical preparations. The haemagglutinin (HA) and trace quantities of viral neuraminidase and phospholipids from the A/Singapore 6/86 virus strain are intercalated within the phospholipid bilayer. The presence of the HA is necessary to enhance the immunopotentiating effect to antigen associated with IRIV The excellent characteristics of IRIVs as adjuvants have been demonstrated in several systems. IRIVs as alternative adjuvant system for human use are registered by most European, Asian and American countries in commercial hepatitis A and influenza vaccines. IRIVs were first used in the manufacture of a hepatitis A vaccine. This contains formalin-inactivated and highly purified hepatitis A virus (HAV) of strain RG-SB, cultured in human diploid cells, which is coupled to the IRIV vesicle. For a new influenza vaccine the surface spikes (HA and NA) of three currently circulating influenza strains were jointly inserted into the vesicle membrane of the IRIVs and successfully tested clinically. In Epaxal Berna, the first commercially available liposomal vaccine is expected to be the inactivated hepatitis A virus adsorbed to IRIV particles. In the virosomal hepatitis A vaccine, the antigen is believed to be attached to the IRIV by interacting with phospholipids which are considered to correspond to its natural receptor on hepatocytes. The present investigation includes data based on light scattering measurements which show the binding of the virions to vesicles.
Glück
R
R
Swiss Serum and Vaccine Institute, Berne.
Wälti
E
E
D000276:Adjuvants, Immunologic; D000818:Animals; D002138:Calibration; D003902:Detergents; D022362:Hepatitis A Vaccines / Q000737:chemistry* / Q000276:immunology*; D006507:Hepatovirus / Q000648:ultrastructure; D006801:Humans; D010316:Particle Size
D000276:Adjuvants, Immunologic; D003902:Detergents; D022362:Hepatitis A Vaccines