Means and methods for treating HBV

1. A recombinant vaccination vector expressing

(a) an envelope protein (HBs-antigen) from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and

(b) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw;

and at least one of the following:

(c) an immunogenic envelope protein (HBs-antigen) from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1; and/or

(d) an immunogenic core protein (HBc-antigen) from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2; and/or

(e) an immunogenic RT domain of a polymerase from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3.

2. The recombinant vaccination vector of claim 1 , wherein the HBs-antigen in (c) and/or the HBc-antigen in (d) is/are from hepatitis B virus genotype C.

3. The recombinant vaccination vector of claim 1 , wherein the immunogenic HBs-antigen in (c) has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4 and/or the immunogenic HBc-antigen in (d) has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 5 and/or the immunogenic RT domain of a polymerase in (e) has at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

4. The recombinant vaccination vector of claim 1 , wherein the core protein from hepatitis B virus serotype ayw in (b) is a C-terminally truncated core protein comprising or consisting of amino acids 1-149 of the HBc-antigen from hepatitis B virus genotype D serotype ayw.

5. The recombinant vaccination vector of claim 1 , further expressing

(f) a CD70.

6. The recombinant vaccination vector of claim 1 , wherein the recombinant vaccination vector is a virus, a virus like particle or a bacterium.

7. The recombinant vaccination vector of claim 1 , wherein the recombinant vaccination vector is a MVA virus.

8. The recombinant vaccination vector of claim 1 , wherein the recombinant vector is an attenuated Salmonella strain, a CMV-, a VSV-based vector, an Adenoviral vector or a Measles vector.

9. A vaccination method against hepatitis B, wherein the method comprises:

(i) administering to a subject

(a′) an envelope protein from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and/or

(b′) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw; and

(ii) administering to the subject a MVA virus expressing

(a) an envelope protein (HBs-antigen) from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein;

and a MVA virus expressing

(b) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw.

10. A vaccination method against hepatitis B, wherein the method comprises:

(i) administering a subject

(a′) an envelope protein from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and/or

(b′) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw; and

(ii) administering to the subject a MVA virus expressing

(a) an envelope protein (HBs-antigen) from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and

(b) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw.

11. The method according to claim 10 , wherein the vaccination method is preferably a method for therapeutic vaccination.

12. The method according to claim 10 , wherein (i) of the vaccination method is a priming step and (ii) of the vaccination method is a boosting step.

13. The method according to claim 10 , wherein the envelope protein and/or the core protein in (i) is co-administered with at least one adjuvant, wherein the adjuvant is preferably selected from the group consisting of poly[di(sodium carboxylatoethylphenoxy)]phosphazene (PCEP), an immune stimulatory oligonucleotide, a toll like receptor (TLR) agonist, a saponin or combinations thereof, wherein the TLR agonist is preferably a TLR 3 agonist, a TLR 4 agonist, a TLR 7 agonist, a TLR 8 agonist, or a TLR 9 agonist, and wherein the immune stimulatory oligonucleotide is preferably poly I/C, CpG, a RIG-I ligand, a STING ligand, cyclic di-AMP, cyclic di-CMP, cyclic di-GMP, a TLR 7 agonist, a TLR 8 agonist, CTA1DD, or dmLT.

14. The method according to claim 10 , wherein (i) is conducted at least about 1 day before conducting (ii), preferably at least about 5 days, preferably at least about 1 week, preferably about 1 week to about 8 weeks, preferably about 2 weeks to about 5 weeks, preferably about 3 weeks to about 4 weeks.

15. The method according to claim 10 , wherein the vaccination method further comprises after (i) and prior to (ii):

(i′) administering to a subject

(a′) an envelope protein from hepatitis B virus genotype A, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and/or

(b′) a core protein (HBc-antigen) from hepatitis B virus genotype D, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw,

wherein (i′) is preferably a boosting step.

16. The method of claim 10 , wherein administration is by a parenteral or mucosal route.

17. A vaccine or a pharmaceutical composition comprising the recombinant vaccination vector of claim 1 .

18. The vaccine of claim 17 , wherein the recombinant vaccination vector is a MVA virus or a Salmonella strain.

19. The vaccine of claim 17 , wherein the vaccine is a parenteral or mucosal vaccine.

20. A kit comprising:

(i) a protein composition comprising:

(a) an envelope protein from hepatitis B virus genotype A, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and/or

(b) a core protein (HBc-antigen) from hepatitis B virus genotype D, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw;

(ii) the vaccine of claim 17 .

21. An expression cassette comprising nucleic acids encoding:

(a) an envelope protein (HBs-antigen) from hepatitis B virus serotype adw, wherein the envelope protein is preferably a small or large envelope protein from hepatitis B virus genotype A serotype adw, wherein the small or large envelope protein is preferably a small envelope protein; and

(b) a core protein (HBc-antigen) from hepatitis B virus serotype ayw, wherein the core protein is preferably from hepatitis B virus genotype D serotype ayw;

and at least one of the following:

(c) an immunogenic envelope protein (HBs-antigen) from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1; and/or

(d) an immunogenic core protein (HBc-antigen) from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2; and/or

(e) an immunogenic RT domain of a polymerase from hepatitis B virus having at least 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 3.