Influenza vaccines
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.