Influenza vaccines

Abstract

An influenza vaccine comprising an influenza hemagglutinin-containing antigen which is subjected to a treatment at a suitable low pH or other suitable conditions to obtain a suitable degree of loss of potency, and the method of making it are provided. The vaccine not only induces an increased cross-reactive immune response and cross protection, but can also induce a strain-specific immune response and protection like current inactivated vaccines. A method of administering influenza vaccines is also provided to induce an increased cross-reactive immune response and cross protection, which is especially suitable for use in emergency situations such as a pandemic.

1 . An influenza vaccine comprising at least one influenza hemagglutinin-containing antigen, wherein said antigen is subjected to a treatment at a suitable low pH or other suitable conditions to obtain a suitable degree of loss of potency; wherein said vaccine induces an increased cross-reactive immune response and cross protection. 
     
     
         2 . The influenza vaccine of  claim 1 , wherein said vaccine comprises at least two said antigens selected from a group comprising H1 and H3 subtypes of influenza A virus. 
     
     
         3 . The influenza vaccine of  claim 1 , wherein said vaccine comprises at least three said antigens selected from a group comprising at least two clades from the first phylogenetic group and at least one clade from the second phylogenetic group, wherein each said antigen is selected from a separate clade. 
     
     
         4 . The influenza vaccine of  claim 1 , wherein said antigen is inactivated or recombinant. 
     
     
         5 . The influenza vaccine of  claim 1 , wherein said antigen is a live virus, and said live virus is inactivated after said treatment. 
     
     
         6 . The influenza vaccine of  claim 1 , wherein said suitable low pH ranges from 3.0 to 6.8 and preferably 4.5 to 6.5. 
     
     
         7 . The influenza vaccine of  claim 1 , wherein said treatment at a suitable low pH is conducted at a temperature ranging from 0 to 37° C. 
     
     
         8 . The influenza vaccine of  claim 1 , wherein said treatment at a suitable low pH is conducted at 0-25° C. 
     
     
         9 . The influenza vaccine of  claim 1 , wherein said antigen exhibits no or less than 2-fold reduction in hemagglutination activity after said treatment. 
     
     
         10 . The influenza vaccine of  claim 1 , wherein said suitable degree of loss of potency ranges from 1 to 100%. 
     
     
         11 . The influenza vaccine of  claim 1 , wherein said suitable degree of loss of potency ranges from 10 to 50%. 
     
     
         12 . The influenza vaccine of  claim 11 , wherein said treatment at a suitable low pH is conducted at 0-25° C. 
     
     
         13 . The influenza vaccine of  claim 1 , wherein said other suitable conditions comprise a suitable high temperature ranging from 37 to 80° C. 
     
     
         14 . The influenza vaccine of  claim 1 , wherein said loss of potency is indicated by a functionally equivalent alternative measurement for antigenic or structural changes. 
     
     
         15 . The influenza vaccine of  claim 1 , wherein said vaccine induces an increased immune response against HA2. 
     
     
         16 . The influenza vaccine of  claim 1 , wherein said vaccine is formulated to meet the potency standard for induction of a strain-specific immune response and protection. 
     
     
         17 . The influenza vaccine of  claim 1 , wherein said vaccine further comprises an adjuvant. 
     
     
         18 . A method for inducing an increased cross-reactive immune response and cross protection against influenza viruses in a human or animal by administering an effective dose of said influenza vaccine of  claim 1 . 
     
     
         19 . A method for inducing both a strain-specific immune response and protection and an increased cross-reactive immune response and cross protection against influenza viruses in a human or animal by administering an effective dose of said influenza vaccine of  claim 16 . 
     
     
         30 . A method for administering an influenza vaccine comprising at least one influenza hemagglutinin-containing antigen to a human or animal, where said vaccine induces an increased cross-reactive immune response and cross protection; wherein said method comprises:
 a. Adding an acidic solution to said vaccine to adjust the pH of said vaccine to a suitable low pH, wherein said suitable low pH is selected from the range of 3.0-6.8, and preferably 4.5-6.5,   b. Keeping said vaccine at a suitable temperature for a suitable period of time, wherein said suitable temperature is selected from the range of 0 to 37° C. and preferably 0 to 25° C.,   c. Optionally adding a basic solution to said vaccine to adjust the pH of said vaccine back to the original or physiological level, and   d. Administering said vaccine to a human or animal, wherein said antigen obtains a suitable degree of loss of potency ranging from 1 to 100% and preferably from 10 to 50%.   
     
     
         31 . A kit comprising:
 a. an influenza vaccine comprising at least one influenza hemagglutinin-containing antigen,   b. An acidic solution in a container, wherein said acidic solution is preferably a low pH buffer, and   c. A basic solution in a container, wherein said basic solution is preferably a buffer at a basic pH.