Influenza viruses vary every year. Sometimes it threatens mankind with the interval of 10 to 40 years, when the viruses have big changes.
The usual variation is a little different in appearance from the existing gene, from small ‘a’ to capital ‘A’, but sometime they have a big change like from alphabet ‘A’ to alphabet ‘B’. It means new virus has occurred. Therefore, the vaccine should be continuously developed in preparation for such a mutation.
All of the influenza that killed many people was caused by big changes of virus. For example, there was the Spanish influenza that killed 25 million people in 1918. It also includes the Asian influenza that killed 1 million people in 1957, the Hong Kong influenza that killed 70 million people in 1968, and the Russian influenza in 1977.