Reducing interference between oil-containing adjuvants and surfactant-containing antigens
Inclusion of fatty adjuvants in vaccine compositions can cause difficulties with certain antigenic components, particularly with antigens that include a surfactant component. A method for preparing an immunogenic composition comprising an antigen and a fatty adjuvant involves purification of the antigen substantially in the absence of surfactant. Where surfactants cannot be avoided, the following are combined: (i) an antigen component that includes a surfactant and (ii) a fatty adjuvant component, to give a composition in which the weight ratio of said fatty adjuvant to said surfactant is less than 1000:1.
1 . A process for preparing an immunogenic composition, comprising the steps of combining
(i) an antigen component that includes a surfactant and
(ii) a fatty adjuvant component,
to give a composition in which the weight ratio of the fatty adjuvant to the surfactant is less than 1000:1.
2 . An immunogenic composition, wherein:
(a) the composition comprises an antigen component and a fatty adjuvant component;
(b) the antigen component includes a surfactant; and
(c) the weight ratio of the fatty adjuvant to the surfactant is less than 1000:1.
3 . The composition of claim 2 , wherein the fatty adjuvant comprises a metabolisable oil.
4 . The composition of claim 3 , wherein the fatty adjuvant comprises a sub-micron oil-in-water emulsion of squalene and polysorbate 80.
5 . The composition of claim 2 , wherein the fatty adjuvant comprises a molecule comprising a fatty acid moiety.
6 . The composition of claim 5 , wherein the fatty adjuvant is a 3-deoxyacylated monophosphoryl lipid A (‘3D-MPL’).
7 . The composition of claim 6 , wherein the 3D-MPL is a mixture of molecules varying by their acylation.
8 . The composition of claim 6 , wherein the fatty adjuvant includes:
9 . The composition of claim 6 , wherein the 3D-MPL is in the form of particles.
10 . The composition of claim 9 , wherein the particles can be filter sterilised.
11 . The composition of claim 6 , wherein the 3D-MPL is in combination with an aluminium salt.
12 . The composition of claim 11 , wherein the aluminium salt is an aluminium phosphate.
13 . The composition of claim 12 , wherein the 3D-MPL is adsorbed onto the aluminium salt.
14 . The composition of claim 2 , wherein the surfactant is a polyoxyethylene sorbitan ester.
15 . The composition of claim 14 , wherein the ester is polysorbate 20.
16 . The composition of claim 2 , wherein the concentration of surfactant no more than 50 μg/ml.
17 . The composition of claim 2 , wherein the antigen is a viral surface antigen.
18 . The composition of claim 17 , wherein the antigen is a particulate hepatitis B surface antigen (‘HBsAg’), purified in the presence of surfactant.
19 . The composition of claim 18 , wherein the HBsAg is expressed in a yeast cell.
20 . The composition of claim 19 , wherein the yeast is a Saccharomyces cerevisiae.
21 . The composition of claim 18 , wherein the HBsAg is non-glycosylated and/or includes phosphatidylinositol.
22 . The composition of claim 18 , wherein the HBsAg is from subtype adw2 of hepatitis B virus.
23 . The composition of claim 2 , wherein the antigen is a hybrid protein comprising a viral surface antigen and a heterologous antigen.
24 . The composition of claim 23 , wherein the viral surface antigen is HBsAg and the heterologous antigen is a malaria antigen.
25 . The composition of claim 23 , wherein the hybrid protein comprises HBsAg and a fragment of the circumsporozoite protein of Plasmodium falciparum.
26 . The composition of claim 25 , wherein the hybrid protein comprises a C-terminal portion of a P. falciparum circumsporozoite protein of Plasmodium falciparum , four or more 0 tandem repeats of the circumsporozoite protein immunodominant region, and HBsAg.
27 . The composition of claim 2 , wherein the weight ratio of the fatty adjuvant to the surfactant is less than 500:1.
28 . The composition of claim 2 , wherein the weight ratio of the fatty adjuvant to the surfactant is less than 50:1.
29 . The composition of claim 2 , wherein the fatty adjuvant is a 3D-MPL and the weight ratio of the fatty adjuvant to the surfactant is between 2.5:1 and 25:1.
30 . The composition of claim 2 , wherein the composition has an osmolality of between 200 mOsm/kg and 400 mOsm/kg.
31 . The composition of claim 2 , wherein the composition includes a phosphate buffer.
32 . The composition of claim 2 , wherein the composition has a pH between 6.0 and 7.0.
33 . (canceled)
34 . The process of claim 1 , wherein the antigen component is an HBsAg component that includes polysorbate 20 and the fatty adjuvant component comprises 3D-MPL adsorbed to an aluminium phosphate, wherein the weight ratio of 3D-MPL to polysorbate 20 in the composition is less than 1000:1.
35 . The immunogenic composition of claim 2 , wherein:
(a) the composition comprises HBsAg, polysorbate 20, 3D-MPL and an aluminium phosphate adjuvant; and
(b) the weight ratio of the 3D-MPL to polysorbate 20 is less than 1000:1.
36 . A process for preparing an immunogenic composition, wherein: (a) the composition comprises an antigen and a fatty adjuvant; and (b) the antigen is purified substantially in the absence of surfactant.