CHANGING TH1/TH2 BALANCE IN SPLIT INFLUENZA VACCINES WITH ADJUVANTS
The invention seeks to avoid components in split vaccines that could cause an excessive Th2 response. Thus the invention provides an immunogenic composition comprising a split influenza virus antigen and a Th1 adjuvant, wherein the antigen is preferably prepared from a virus grown in cell culture (e.g., it is free from egg proteins).
1 . An immunogenic composition comprising a split influenza virus antigen and a ThI adjuvant, wherein the antigen is prepared from a virus grown in cell culture and does not include any egg proteins.
2 . The method of claim 1 , wherein the influenza virus antigen is from a H1, H2, H3, H5, H7 or H9 influenza A virus subtype.
3 . The composition of claim 1 , wherein the composition is free from ovalbumin, ovomucoid and chicken DNA.
4 . The composition of claim 1 , wherein the virus is grown on a cell culture of a cell line selected from the group consisting of: MDCK; Vero; and PER.C6.
5 . The composition of claim 1 , wherein the composition contains less than 10 ng of cellular DNA from the cell culture host.
6 . The composition of claim 1 , wherein the composition contains less than 10 ng of DNA that is 100 nucleotides or longer.
7 . The composition of claim 1 , wherein the composition contains between 0.1 and 20 μg of haemagglutinin per viral strain.
8 . The composition of claim 1 , wherein the adjuvant includes a tocopherol.
9 . The composition of claim 8 , wherein the tocopherol is DL-[alpha]-tocopherol.
10 . The composition of claim 1 , wherein the adjuvant is in the form of an oil-in-water emulsion.
11 . The composition of claim 10 , wherein the emulsion has droplets with a sub-micron diameter.
12 . The composition of claim 1 , wherein the influenza virus antigen is prepared from an influenza virus having one or more RNA segments from an A/PR/8/34 influenza virus.
13 . The composition of claim 1 , wherein the influenza virus antigen is prepared from an influenza virus obtained by reverse genetics techniques.
14 . The composition of claim 1 , wherein the cell culture is a microcarrier culture, an adherent culture, or a suspension culture.
15 . The composition of claim 1 , wherein the cell culture is serum-free.
16 . The composition of claim 1 , wherein the adjuvant comprises a 3-O-deacylated monophosphoryl lipid A (3dMPL).
17 . The composition of claim 16 , wherein at least 10% by weight of the 3dMPL is the hexaacyl chain form.
18 . The composition of claim 16 , wherein the 3dMPL is in the form of particles with a diameter <150 nm.
19 . The composition of claim 1 , being substantially free from mercurial material.
20 . The composition of claim 1 , including between 1 and 20 mg/ml sodium chloride.
21 . The composition of claim 1 , having an osmolality between 200 and 400 m[theta]sm/kg.
22 . The composition of claim 1 , including one or more buffer(s).
23 . The composition of claim 22 , wherein the buffer(s) include: a phosphate buffer; a Tris buffer; a borate buffer; a succinate buffer; a histidine buffer; or a citrate buffer.
24 . The composition of claim 1 , having a pH between 5.0 and 8.1.
25 . The composition of claim 1 , containing <1 endotoxin unit per dose.
26 . The composition of claim 1 , being gluten free.
27 . The composition of claim 1 , wherein the composition includes two influenza A strains and one influenza B strain.
28 . The composition of claim 1 , wherein the composition is a monovalent vaccine against a pandemic influenza virus strain.
29 . An immunogenic composition comprising a split influenza virus antigen and an oil-in-water emulsion, wherein (a) the antigen is prepared from a virus grown in cell culture, and (b) the oil-in-water emulsion includes a tocopherol.
30 . The composition of claim 11 , wherein the emulsion includes squalene, a tocopherol, and polysorbate 80.