Composition and uses thereof
The present invention provides a particle comprising a fusion protein, wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7), some or all of the C-terminus of the CS protein from Plasmodium falciparum and a hepatitis B surface antigen, and wherein the particle comprises no, or substantially no, free hepatitis B surface antigen protein, and uses thereof.
1. A virus-like particle comprising a fusion protein, wherein the fusion protein comprises at least one NANP repeat (SEQ ID NO: 7), and the C-terminus of the CS protein from Plasmodium falciparum comprising the sequence :
(SEQ ID NO: 6)
NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKIEKEYLN
KIQNSLSTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICK
MEKCSSVFN VVNSSIGI;
or the sequence
(SEQ ID NO: 4)
NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKHIKEYLN
KIQNSLSTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICK
MEKCSSV,
or a conservative substitution variant of SEQ ID No: 6 or SEQ ID NO: 4 with 95% or more sequence identity therewith; and HBsAg, wherein the virus-like particle comprises no free HBsAg.
2. The virus-like particle of claim 1 comprising at least 10 NANP repeats (SEQ ID NO: 13).
3. The virus-like particle of claim 1 , wherein the particle comprises at least about 40% or more by mass of its proteinaceous material, the proteinaceous material being derived from Plasmodium falciparum.
4. The virus-like particle of claim 1 comprising a fusion protein consisting of:
the sequence of SEQ ID NO: 1 (R21);
the sequence of SEQ ID NO: 2 (RTS); or
a sequence with at least 95%, or more sequence identity with the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.
5. A fusion protein comprising at least one NANP repeat (SEQ ID NO: 7), and the C terminus of the CS protein from Plasmodium falciparum comprising the sequence :
(SEQ ID NO: 6)
NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKIEKEYLN
KIQNSLSTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICK
MEKCSSVFN VVNSSIGI;
or the sequence
(SEQ ID NO: 4)
NKNNQGNGQGHNMPNDPNRNVDENANANSAVKNNNNEEPSDKHIKEYLN
KIQNSLSTEWSPCSVTCGNGIQVRIKPGSANKPKDELDYANDIEKKICK
MEKCSSV;
or a conservative substitution variant of SEQ ID No: 6 or SEQ ID NO: 4 sequence with 95% or more sequence identity therewith; and HBsAg, wherein the fusion protein comprises no free HBsAg.
6. The fusion protein of claim 5 , wherein the fusion protein consists of, a sequence of SEQ ID NO: 1 (R21) or a sequence with at least 95% or more sequence identity with the sequence of SEQ ID NO: 1.
7. The fusion protein of claim 5 , wherein the fusion protein is expressed in a Saccharomyces cerevisiae or Pichia pastoris or a methylotrophic yeast cell.
8. The fusion protein of claim 7 , wherein the methylotrophic yeast cell is Hansenula polymoipha.