Virosome particles comprising antigens from influenza virus and hepatitis b virus
The present invention provides a virosome comprising a virosomal membrane comprising at least one lipid and envelope proteins of an enveloped virus and of the virosome and attached to said envelope proteins. Furthermore, the invention provides a vaccine comprising the virosome of the invention and, a method for the production of a virosome of the invention. Moreover, the invention provides a use of a virosome of the invention for the preparation of a vaccine, e.g. for the prevention or alleviation of a disease related to an HBV infection, and a method for the vaccination of a subject.
1. A virosome comprising:
a virosomal membrane comprising at least one lipid, an envelope protein of influenza virus, and an envelope protein of hepatitis B virus (HBV); and
nucleocapsid particles comprising HBc protein of HBV,
wherein the nucleocapsid particles are attached to the envelope proteins of HBV through an interaction between the envelope proteins of HBV and the HBc proteins of HBV, wherein a first plurality of the nucleocapsid particles so attached are located on the inside of the virosome, wherein a second plurality of the nucleocapsid particles so attached are located on the outside of the virosome, wherein the nucleocapsid protein HBc lacks an exposed lipophilic domain, and wherein the virosome is able to induce a therapeutic Th1 response to HBV infection.
2. The virosome of claim 1 , wherein said at least one lipid comprises at least one phospholipid.
3. The virosome of claim 2 , wherein the at least one phospholipid comprises a phospholipid selected from the group consisting of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine.
4. The virosome of claim 1 , wherein the envelope protein of influenza virus is hemagglutinin (HA).
5. The virosome of claim 1 , wherein the envelope protein of HBV is HBs protein.
6. A vaccine comprising the virosome of claim 1 , and a pharmaceutically acceptable carrier or diluent and/or an adjuvant.
7. The vaccine of claim 6 , wherein the adjuvant is RC529.
8. A method for vaccinating a subject for the prevention, alleviation or treatment of an HBV infection, the method comprising:
administering the virosome of claim 1 to the subject.
9. The method according to claim 8 , wherein the virosome is in combination with a pharmaceutically acceptable carrier or diluent and/or an adjuvant.
10. The virosome of claim 1 , wherein the envelope protein of influenza virus is neuraminidase (NA).
11. The virosome of claim 1 , wherein the virosomal membrane comprises a second envelope protein of influenza virus.
12. The virosome of claim 11 , wherein the envelope protein of influenza virus and second envelope protein of influenza virus are hemagglutinin (HA) and neuraminidase (NA).
13. A virosome comprising:
a virosomal membrane comprising at least one lipid, at least one envelope protein of influenza virus, and hepatitis B virus (HBV) envelope protein HBs;
nucleocapsid particles comprising HBV nucleocapsid protein HBc attached to the HBs protein, such that the HBc protein is located on the inside of the virosome; and
nucleocapsid particles comprising HBV nucleocapsid protein HBc attached to the HBs protein, such that the HBc protein is located on the outside of the virosome,
wherein nucleocapsid protein HBc lacks an exposed lipophilic domain, and
wherein the virosome is able to induce a therapeutic Th1 response to HBV infection in a subject to which the virosome has been administered.
14. The virosome of claim 13 , wherein the HBV envelope protein HBs comprises a mammalian glycosylation pattern, and wherein the HBV nucleocapsid protein HBc is bacterially-produced.
15. The virosome of claim 13 , wherein the lipid is phosphatidylcholine, and wherein the envelope protein of influenza virus is hemagglutinin (HA).
16. The virosome of claim 15 , wherein the lipid:protein ratio in the virosome is about 5:1, wherein the portion of phosphatidylcholine in the virosome is 22% by weight, and wherein the ratio of HA:HBs:HBc is 1:1:1.
17. The virosome of claim 13 , wherein the HBV nucleocapsid protein HBc is selected from the group consisting of serotype ayw HBc, serotype adw HBc, full-size HBc, and truncated HBc.
18. The virosome of claim 13 , wherein the HBV envelope protein HBs is produced and glycosylated in a cell selected from the group consisting of CHO cells and yeast cells.