Novel vaccine composition

Abstract

An inactivated influenza virus preparation is described which comprises a haemagglutinin antigen stabilised in the absence of thiomersal, or at low levels of thiomersal, wherein the haemagglutinin is detectable by a SRD assay. The influenza virus preparation may comprise a micelle modifying excipient, for example α-tocopherol or a derivative thereof in a sufficient amount to stabilise the haemagglutinin.

1 - 35 . (canceled) 
     
     
         36 . An influenza vaccine comprising an inactivated influenza virus preparation and an adjuvant, wherein said inactivated influenza virus preparation comprises hemagglutinin antigen (HA), 0 μg/ml to 5 μg/ml of thiomersal and at least one stabilising excipient, and wherein said adjuvant is selected from the group of: an oil in water emulsion, a non-toxic derivative of lipid A, a saponin or derivative thereof, and a combination of two or more of said adjuvants. 
     
     
         37 . The influenza vaccine according to  claim 36 , wherein said non-toxic derivative of lipid A is 3D-MPL. 
     
     
         38 . The influenza vaccine according to  claim 36 , wherein 3D-MPL is in the form of an emulsion having a small particle size less than 0.2 μm in diameter. 
     
     
         39 . The influenza vaccine according to  claim 36 , wherein said said excipient comprises α-tocopherol or a derivative thereof. 
     
     
         40 . The influenza vaccine according to  claim 36 , wherein said excipient comprises α-tocopherol succinate. 
     
     
         41 . The influenza vaccine according to  claim 36 , wherein said excipient comprises a positively or negatively or zwitterionic charged amphiphilic molecule. 
     
     
         42 . The influenza vaccine according to  claim 36 , wherein said excipient comprises a non-ionic amphiphilic molecule from the group of: octyl- or nonylphenoxy polyoxyethanols, polyoxyethylene sorbitan esters and polyoxyethylene ethers or esters of general formula (I):
   HO(CH2CH2O) n -A-R   (I)   wherein n is 1-50, A is a bond or —C(O)—, R is C 1-50  alkyl or phenyl C 1-50  alkyl; and combinations of two or more of these.   
     
     
         43 . The influenza vaccine according to  claim 42 , wherein said non-ionic amphiphilic molecule is selected from the group of: Triton X-45, t-octylphenoxy polyethoxyethanol (Triton X-100™), Triton X-102, Triton X-114, Triton X-165, Triton X-205, Triton X-305, Triton N-57, Triton N-101, Triton N-128, Breij 35, polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-stearyl ether (steareth 9), polyoxyethylene sorbitan ester, and polyoxyethylene sorbitan monooleate (Tween 80™). 
     
     
         44 . The influenza vaccine according to  claim 42 , wherein said non-ionic amphiphilic molecule is selected from the group: Triton X-100™, Tween 80™, and a combination of both. 
     
     
         45 . The influenza vaccine according to  claim 39 , wherein the a-tocopherol or derivative thereof is present at a concentration between 1 μg/ml and 10 mg/ml. 
     
     
         46 . The influenza vaccine according to  claim 36 , wherein the α-tocopherol is present at a concentration between 1 μg/ml and 10 mg/ml. 
     
     
         47 . The influenza vaccine according to  claim 36 , wherein said influenza virus antigen preparation is selected from the group consisting of: split virus antigen preparations, subunit antigens, chemically or otherwise inactivated whole virus and recombinantly produced haemagglutinin antigen. 
     
     
         48 . The influenza vaccine according to  claim 36 , wherein the concentration of haemagglutinin antigen for each strain of influenza is 1-1000 μg per ml, as measured by a Single radial Immunodiffusion (SRD) assay. 
     
     
         49 . The influenza vaccine according to  claim 36 , wherein said influenza virus antigen preparation is derived from the embryonated egg method or derived from cell culture. 
     
     
         50 . The influenza vaccine according to  claim 36 , wherein said influenza virus antigen preparation comprises a haemagglutinin antigen that is produced recombinantly. 
     
     
         51 . An inactivated influenza virus preparation, comprising hemagglutinin antigen (HA), 0 μg/ml to 5 pg/ml of thiomersal, and at least one of α-tocopherol or a derivative thereof in an amount sufficient to stabilize said HA. 
     
     
         52 . The inactivated influenza virus preparation of  claim 50 , wherein said influenza virus is selected from the group of: split virus antigen preparations, subunit antigens, chemically or otherwise inactivated whole virus, and recombinantly produced haemagglutinin antigen. 
     
     
         53 . The inactivated influenza virus preparation of  claim 50 , wherein said preparation comprises α-tocopherol or α-tocopherol succinate. 
     
     
         54 . The inactivated influenza virus preparation of  claim 50 , wherein the at least one of α-tocopherol or a derivative thereof is present in an amount such that the HA of said preparation remains stable for at least 6 months after said preparation is produced as determined by the presence of an amount of HA detectable by Single radial Immunodiffusion (SRD) assay. 
     
     
         55 . The inactivated influenza virus preparation of  claim 50 , wherein the at least one of a-tocopherol or a derivative thereof further comprises at least one of a non-ionic amphiphilic molecule from the group of: octyl- or nonylphenoxy polyoxyethanols, polyoxyethylene sorbitan esters and polyoxyethylene ethers or esters of general formula (I):
   HO(CH2CH2O) n -A-R   (I)   wherein n is 1-50, A is a bond or —C(O)—, R is C 1-50  alkyl or phenyl C 1-50  alkyl; and combinations of two or more of these.   
     
     
         56 . The inactivated influenza virus preparation of  claim 55 , wherein said non-ionic amphiphilic molecule is selected from the group of: Triton X-45, t-octylphenoxy polyethoxyethanol (Triton X-100™), Triton X-102, Triton X-114, Triton X-165, Triton X-205, Triton X-305, Triton N-57, Triton N-101, Triton N-128, Breij 35, polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-stearyl ether (steareth 9), polyoxyethylene sorbitan ester, and polyoxyethylene sorbitan monooleate (Tween 80™). 
     
     
         57 . The inactivated influenza virus preparation of  claim 55 , wherein said non-ionic amphiphilic molecule is selected from the group: Triton X-100™, Tween 80™, and a combination of both. 
     
     
         58 . The inactivated influenza virus preparation according to  claim 50 , wherein the α-tocopherol or derivative thereof is present at a concentration between 1 pg/ml and 10 mg/ml. 
     
     
         59 . A vaccine comprising the inactivated influenza virus preparation of  claim 50 . 
     
     
         60 . An influenza vaccine according to  claim 58 , wherein the vaccine additionally comprises an adjuvant.