What’s in a Flu Vaccine

Pennsylvania: If you’re a person that gets a flu shot every year, chances are you have received it by now, along with the millions of others in the United States who have also been vaccinated. According to Centers for Disease Control survey data collected through early November 2016, forty percent of people have received a flu vaccine so far this year. Although getting the shot is simple enough, what goes into the vaccine, from a biological perspective to a policy point of view, is anything but. Flu vaccines work by priming the immune system with purified proteins from the outer layer of killed flu viruses. This induces immune cells to make antibodies that stop foreign invaders from infecting cells. Educating the immune system in this way readies it to attack flu viruses if the body sees them again.

Twice a year the World Health Organization (WHO) recommends viral strains to put in vaccines for the Northern and Southern Hemisphere flu seasons. Their last meeting was in September 2016. They chose the H3N2, H1N1, and Flu B viral strains for the Southern Hemisphere vaccine, which will be given as their winter season approaches in 2017. WHO will meet next in February 2017 to choose the viral strains for the Northern Hemisphere vaccine, which will be administered prior to our 2017-2018 winter flu season.
Basic research from the lab of Scott Hensley, PhD, an associate professor of Microbiology, is changing how WHO makes their decision about which viral strains will go in upcoming flu vaccines. This has the potential to affect the health of millions of people worldwide. 
The Hensley lab studies viral evolution in real time. “Flu viruses are constantly acquiring mutations in the proteins of their outer layer, and many of these mutations prevent the binding of antibodies elicited by prior influenza exposures,” Hensley said.
Complicating matters is “that all of us respond differently to the flu vaccine, depending on our individual immune histories,” Hensley said. “We now know that early childhood viral exposures impact how we respond to flu vaccines and flu infections as adults.” 
Hensley and colleagues discovered that these early childhood “immunological imprints” affect how people respond to the current H1N1 vaccine. The vaccine being used in 2016 in the Northern Hemisphere contains a weakened HINI flu strain from 2009.
For some people who are middle-aged now, born prior to 1985, their first exposure to the flu was from an H1N1 virus that emerged in 1977.  This 1977 virus elicited long-lasting immune responses that were beneficial during the 2009 H1N1 swine flu pandemic, since the 1977 and 2009 H1N1 viruses share some similarities. This meant that people who were exposed to the 1977 strain were less likely to be affected by H1N1 in 2009. However, this benefit vanished in 2013 when H1N1 viruses acquired a new mutation in a protein on its outer layer.
“This explains why middle-aged people were preferentially affected by the flu during the 2013-2014 season,” Hensley said. His lab showed that the new mutation in the H1N1 strain allowed viruses to avoid the immune response elicited in middle-aged adults.
They conducted tests against this outer layer protein using blood drawn from 323 different-aged individuals prior to the 2013-2014 season. They found that many middle-aged people produced antibodies that recognized the H1N1 vaccine strain but failed to recognize the 2013-2014 circulating H1N1 strain with the mutation. Individuals with these types of antibodies were susceptible to the mutated 2013-14 H1N1 virus.
Initially, WHO did not recognize that the H1N1 virus circulating in 2013-2014 was distinct compared to the H1N1 vaccine strain. Part of the reason for this oversight is because WHO relies on data from ferrets never exposed to the flu virus to determine if new viral mutations are important. In previous work, Hensley and colleagues found that ferrets mount different antibody responses compared to most humans because ferrets used for these studies live in captivity and have never been exposed to flu viruses in the past.
According to WHO, upcoming flu vaccines will contain the updated H1N1 component so that the vaccine will work effectively in individuals of all ages.  
These changes have already been made for the Southern Hemisphere vaccine and should help for their upcoming flu season, says Hensley, but for the Northern Hemisphere vaccine that most of us have already taken, and does not contain the update, only time will tell regarding the outcome.
Perhaps by applying basic immunological research like that in the Hensley lab, humans may be able to catch up a little to the rapid pace of viral evolution.