Use Of An Influenza Virus, An Oil-In-Water Emulsion Adjuvant, To Induce Cd4 T-Cell And/Or Improved B-Memory Cell Response

Abstract

The present invention relates to influenza vaccine formulations and vaccination regimes for immunising against influenza disease. In particular the invention relates to vaccine formulations comprising an oil-in-water emulsion adjuvant and optionally 3D-MPL, their use in medicine, in particular their use in augmenting immune responses to influenza antigens, and to methods of preparation, wherein the oil in water emulsion comprises a sterol, a metabolisable oil and an emulsifying agent.

1 . A method of inducing a response chosen from the group of: (i) and improved CD4 T-cell immune response; (ii) an improved B-memory cell response in a human; (iii) an improved humoral response; and (iv) any combination of at least two of said response(s), said method comprising the step of administering to the human an immunogenic composition comprising (a) an influenza virus or antigenic preparation thereof, and (b) an oil-in-water emulsion adjuvant wherein said oil-in-water emulsion comprises a metabolisable oil, a sterol and/or alpha-tocopherol, and an emulsifying agent. 
     
     
         2 . A method of vaccinating against influenza a human elderly patient of 50 years or above, or of 65 years or above, said method comprising the step of administering to the patient an immunogenic composition comprising an influenza virus or antigenic preparation thereof an an an oil-in-water emulsion adjuvant, wherein said oil-in-water emulsion comprises a metabolisable oil, a sterol and/or alpha-tocopherol and an emulsifying agent. 
     
     
         3 - 7 . (canceled) 
     
     
         8 . The method according to  claim 1 , wherein said alpha-tocopherol is present in a amount of from about 1.0% to about 20% of the total volume of said immunogenic composition. 
     
     
         9 . The method according to  claim 1 , wherein said alpha-tocopherol is present in an amount of from about 1.0% to about 5.0 % of the total volume of said immunogenic composition. 
     
     
         10 . The method according to  claim 1 , wherein said metabolisable oil is squalene. 
     
     
         11 . The method according to  claim 1 , wherein said metabolisable oil is present in amount of from about 0.5% to about 20% of the total volume of said immunogenic composition. 
     
     
         12 . The method according to  claim 11 , wherein said metabolisable oil is present in an amount of from about 1.0% to about 10% of the total volume of said immunogenic composition. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . The method according to  claim 10 , wherein the ratio of squalene: alpha-tocopherol is equal or less than 1. 
     
     
         17 . The method according to  claim 1 , wherein said emulsifying agent is Tween 80. 
     
     
         18 . The method according to  claim 17 , wherein said emulsifying agent is present at an amount of from about 0.01 to about 5.0% by weight (w/w) of said immunogenic composition. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The method according to  claims 1 , wherein the immunogenic composition further comprises a TLR-4 ligand. 
     
     
         22 - 26 . (canceled) 
     
     
         27 . The method according to  claims 1 , wherein said CD4 T-cell immune response involves the induction of a cross-reactive CD4 T helper response. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . A method of revaccinating a human previously vaccinated against influenza virus, said method comprising the step of administering to said human an immunogenic composition comprising an influenza virus or antigenic preparation thereof and wherein the immunogenic composition for said previous vaccination comprises an influenza virus or antigenic preparation therof and an oil-in-water emulsion adjuvant, said adjuvant a metabolisable oil, a sterol and/or alpha-tocopherol, and an emulsifying agent. 
     
     
         31 . (canceled) 
     
     
         32 . The method according to  claim 30 , wherein said immunogenic composition for revaccination comprises an adjuvant, and wherein said adjuvant is chosen from the group of: oil-in-water emulsion adjuvant, an aluminium adjuvant, a TLR-4 ligand, and a saponin and a combination of an oil-in-water emulsion adjuvant and a TLR-4 ligand. 
     
     
         33 . The method according to  claims 32 , wherein said oil-in-water emulsion adjuvant for revaccination comprises a metabolisable oil, a sterol and/or alpha-tocopherol, and an emulsifying agent. 
     
     
         34 . The method according to  claim 30 , wherein said immunogenic composition for revaccination contains an influenza virus or antigenic preparation thereof that shares at least one property chosen from the group of: i) common CD4 T-cell epitopes, and ii) common B cell epitopes with the influenza virus or antigenic preparation thereof used for the first vaccination. 
     
     
         35 . The method according to  claim 30 , wherein the immunological response following revaccination is any or two or all of the following: (i) an improved CD4 response against the influenza virus or antigenic preparation thereof, (ii) an improved humoral response, or (iii) an improved B cell memory response. 
     
     
         36 . A method of protecting a uman against an influenza infection caused by a variant influenza strain, said method comprising the step of administering to said human an immunogenic composition comprising: (a) an influenza virus or antigenic preparation thereof from a first influenza strain, and (b) an oil-in-water emulsion adjuvant, wherein said oil-in-water emulsion adjuvant comprises a metabolisable oil, a sterol and/or alpha-tocopherol and an emulsifying agent. 
     
     
         37 . The method according to  claim 36 , wherein said immunogenic composition further comprises a TLR-4 ligand. 
     
     
         38 . The method according to  claim 1 , wherein said immunogenic composition conatins an influenza virus or antigenic preparation thereof from one influenza strain, two different influenza strains, or three different influenza strains. 
     
     
         39 . (canceled) 
     
     
         40 . The method according to  claim 39 , wherein at least one strain is associated with a pandemic outbreak, or has the potential to be associated with, a pandemic outbreak. 
     
     
         41 . (canceled) 
     
     
         42 . The method according to  claim 38 , wherein the first vaccination is made with a split influenza composition containing an influenza strain that could potentially cause a pandemic outbreak, and the revaccination is made with a circulating pandemic strain. 
     
     
         43 . The method according to  claim 1 , wherein said immunogenic composition contains a low dose of HA antigen. 
     
     
         44 . (canceled) 
     
     
         45 . A method of designing a vaccine for influenza diseases known to be cured or treated through a CD4+ T cell activation, said method comprising the steps of:
 1) selecting an antigen containing CD4+ epitopes; and   2) combining said antigen with an oil-in-water emulsion adjuvant, wherein said oil-in-water emulsion adjuvant comprises a metabolisable oil, a sterol and/or alpha-topopherol, and an emulsifying agent, wherein said vaccine upon administration in a said mammal is capable of inducing an enhanced CD4 response against against influenza virus or antigenic preparation thereof in said mammal.   
     
     
         46 . The method according to  claim 1 , wherein said influenza virus is chosen from the group of: a split influenza virus, a whole influenza virus, a sub-unit influenza virus, an influenza virosome, and antigenic preparation thereof. 
     
     
         47 . (canceled)