Manufacture of vaccines that contain both hepatitis b virus surface antigen and surfactant

Abstract

When preparing HBsAg for use in a combination vaccine, it is known to add a non-ionic detergent after the HBsAg has been purified. Adding detergents after purification of HBsAg is not optimal, however, as it requires a separate processing step during manufacture. Thus the invention uses them during HBsAg purification.

1 . A combination vaccine, wherein the vaccine comprises: (i) a non-ionic surfactant, (ii) a purified, recombinant hepatitis B virus (HBV) surface antigen (HBsAg) adsorbed onto an aluminium phosphate adjuvant, and (iii) an antigen from at least one non-HBV pathogen, wherein the non-ionic surfactant is present at <50 μg for every 100 μg of HBsAg. 
     
     
         2 . The combination vaccine of  claim 1 , wherein the HBsAg is prepared by a process in which recombinant HBsAg-expressing yeast cells are disrupted in the presence of the non-ionic surfactant, where the non-ionic surfactant is retained within the HBsAg particle, and wherein the process does not involve a step of adding the non-ionic surfactant as a separate component after HBsAg purification. 
     
     
         3 . The combination vaccine of  claim 1 , wherein the non-ionic surfactant includes poly(oxyethene) residues. 
     
     
         4 . The combination vaccine of  claim 3 , wherein the non-ionic surfactant is a polyoxyethylenesorbitan ester. 
     
     
         5 . The combination vaccine of  claim 4 , wherein the non-ionic surfactant is polysorbate 20. 
     
     
         6 . The combination vaccine of  claim 1 , wherein the non-ionic surfactant is present at <30 μg/ml. 
     
     
         7 . The combination vaccine of  claim 1 , wherein the non-ionic surfactant is present at ≦40 μg for every 100 μg of HBsAg. 
     
     
         8 . The combination vaccine of  claim 1 , wherein the at least one non-HBV pathogens includes  C. diphtheriae  and  C. tetani  and the antigens from these two pathogens are a diphtheria toxoid and a tetanus toxoid. 
     
     
         9 . The combination vaccine of  claim 1 , wherein the HBsAg is non-glycosylated. 
     
     
         10 . The combination vaccine of  claim 1 , wherein the HBsAg is in the form of particles including a lipid matrix comprising phospholipids. 
     
     
         11 . The combination vaccine of  claim 1 , wherein the HBsAg is from HBV subtype adw2. 
     
     
         12 . The combination vaccine of  claim 1 , wherein the HBsAg is present at about 10 μg per dose. 
     
     
         13 . The combination vaccine of  claim 1 , wherein the vaccine includes a Hib conjugate, a meningococcal conjugate, and/or a pneumococcal conjugate. 
     
     
         14 . The combination vaccine of  claim 1 , wherein the vaccine is selected from: a 3-valent HBsAg (Hepatitis B Virus surface antigen), D (diphtheria toxoid), T (tetanus toxoid) composition; a 4-valent HBsAg, D, T, Pw (cellular pertussis antigen) composition; a 5-valent HBsAg, D, T, Pw, Hib (Haemophilusinfluenzae b capsular saccharide) composition; a 7-valent HBsAg, D, T, Pw, Hib, MenA ( Neisseria meningitidis  serogroup A), MenC ( Neisseria meningitidis  serogroup C) composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135 ( Neisseria meningitidis  serogroup W135) composition; a 8-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenY ( Neisseria meningitidis  serogroup Y) composition; a 9-valent HBsAg, D, T, Pw, Hib, MenA, MenC, MenW135, MenY composition; a 4-valent HBsAg, D, T, Pa (acellular pertussis antigen) composition; a 5-valent HBsAg, D, T, Pa, Hib composition; a 5-valent HBsAg, D, T, Pa, poliovirus composition; a 6-valent HBsAg, D, T, Pa, poliovirus, Hib composition; a 7-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC composition; an 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenY composition; a 8-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenW 135 composition; a 10-valent HBsAg, D, T, Pa, poliovirus, Hib, MenC, MenA, MenW135, MenY composition; a 2-valent HBsAg, Hib composition; and a 2-valent HBsAg, hepatitis A virus composition. 
     
     
         15 . The combination vaccine of  claim 1  comprising both aluminium phosphate and aluminium hydroxide adjuvants. 
     
     
         16 . The combination vaccine of  claim 15 , wherein the concentration Al 3+  in the final composition is <5 mg/ml. 
     
     
         17 . A method of raising an immune response in a patient, comprising the step of administering the combination vaccine of  claim 1  to the patient.