Immunopotentiating reconstituted influenza virosomes (IRIVs) and other adjuvants for improved presentation of small antigens.

Synthetic peptides, purified subunits or inactivated small virus particles require immunopotentiation if they are to be effective vaccines. A large range of procedures to enhance immunogenicity has evolved over the last decades: aluminium salts, proteosomes, immunostimulating complexes (ISCOMs), liposomes, conjugation with bacterial products or derivatives, combination with surface-active agents or application of cytokines have been the most described classes of adjuvants. We describe here the design of an inactivated hepatitis A vaccine adjuvanted with immunopotentiating reconstituted influenza virosomes (IRIVs). The formalin-inactivated hepatitis A particles are attached to reconstituted protein-lipid complexes consisting of a mixture of phospholipids and influenza virus glycoproteins. With this new vaccine design we combined different immunostimulating effects: immunopotentiation by phospholipid vesicles, recognition of the haemagglutinin (HA) epitopes by the immune system, binding capacity of HA to sialic acid-containing receptors of macrophages and immunocompetent cells and mediation of entry into the cytoplasm of macrophages by a membrane-fusion event triggered by HA. Hepatitis A seronegative human volunteers received one intramuscular injection with this new vaccine. There were only few mild local reactions and 14 days after vaccination 100% of the subjects were seropositive. Among the individuals (control group) who received an alum-adsorbed vaccine, 88% developed local reactions. The seroconversion rate was 44%. We conclude from these results that the IRIVs provide a new approach to the future design of adjuvanted vaccines.