Influenza vaccines are relatively less effective than other common vaccines, and for a variety of reasons.
The seasonal flu vaccine is less effective than vaccines such as the MMR vaccine, which is about 97% effective in preventing measles, 88% effective in preventing mumps, and 97% effective in preventing rubella. In contrast, the effectiveness of influenza vaccines is usually 40 to 60 percent, and sometimes their effectiveness is reduced by up to 10 percent.
But why are flu vaccines less effective than other common vaccines? This is largely due to the rapid mutation of influenza viruses and the uncertainty about which strains may be circulating in the upcoming flu season. Some vaccine weaknesses may also be due to the way the vaccine is made and certain parts of the flu virus that the vaccine is targeting. But even though the flu vaccine is not perfect, it still provides adequate protection and is worth getting.
According to the Centers for Disease Control and Prevention, the seasonal flu vaccine usually trains the body to fight four types of flu viruses: two influenza A viruses from the H1N1 and H3N2 subtypes and two type B influenza viruses from the Victoria and Yamata. These influenza viruses mutate rapidly from year to year, meaning that their genetic code changes and the proteins on their outer surface change rapidly.
Dr. William Schaffner, an infectious disease specialist at Vanderbilt University, said the flu vaccine works by training the immune system to detect one of these surface proteins, called hemagglutinin (HA). Hemagglutinin appears as bumps on the surface of the virus.
Like the new corona virus spike protein, the hemagglutinin protein of the influenza virus enables it to attach to and enter cells and eventually infect them. The HA protein mutates rapidly and changes every year, making it difficult for the immune system to detect.
Digital display of influenza virus
Another challenge is that influenza vaccines must be made and prepared before the flu season; So scientists are using different strategies to predict which strains of the flu will be circulating in society in the coming months.
Even when the vaccine is ready, the circulating viruses can continue to mutate and sometimes change to such an extent that they do not respond well to the vaccine. In addition, with the onset of the flu season, the flu strains that scientists thought would be the most common strains may sometimes be defeated by other versions of the virus.
To predict which side effects of the flu will prevail next season, more than 140 national flu centers in 113 countries collect samples of people who get the flu during the year and identify those who are actually infected with the flu.
Five WHO-affiliated centers then perform genetic sequencing of the samples, describe the proteins on the surface of the virus, and perform laboratory tests to see how well past vaccines have neutralized circulating influenza strains. They also determine which strains make people sick the most and how fast the different strains spread.
In February, counselors at each center make recommendations on which strains should be considered in the winter flu vaccine for the Northern Hemisphere. In September, they do the same for the southern hemisphere. “Sometimes the right choice is made, and in some cases the flu can escape our expectations,” Schaffner said.
However, even when there is a good match between the strains used in the vaccine and the circulating strains, the effectiveness of the vaccines is usually around 40 to 60%. This relatively low efficacy may be due to the fact that vaccines target only the hemagglutinin protein, rather than targeting multiple spots on the flu virus.
In addition, the immune system can sometimes be weakened due to previous exposure to the flu. According to a report published in the 2013 issue of Clinical Microbiology Reviews, the natural immune response to influenza infection involves the production of antibodies against several proteins on the surface of the virus, not just HA. In contrast, vaccines mainly produce antibodies against HA protein, and it is unclear whether targeting other surface proteins can increase the effectiveness of vaccines.
Our first exposure to the flu in childhood may affect how the immune system responds to vaccination and sometimes to our detriment. After the first exposure to the flu, the body produces memory B cells, which are immune cells that remember the virus and can be reactivated in the future to produce more antibodies.
Some evidence suggests that later, if a person is vaccinated against a flu virus similar (but not identical) to the flu virus they first encountered, the body may reactivate these memory B cells, which produce antibodies that target the target. They have lost themselves.
Many flu vaccines are tested on domestic mice that have never been exposed to the flu before, so it is difficult to know if the vaccine works the same way in humans who have probably been exposed to the flu several times before.
The method of producing more influenza vaccines may also reduce their success. Most flu vaccines contain viruses that have grown in eggs as part of the production process. “You have to slightly modify the virus to grow abundantly in the egg,” explains Schaffner.
There is evidence that when viruses multiply in eggs, they may acquire mutations that cause their genetics to distance themselves from circulating influenza strains. Therefore, when the viruses grown in the egg become inactivated or weakened for the use of influenza vaccines, they are no longer compatible with wild-type influenza viruses.
In general, influenza A (H3N2) viruses mutate more rapidly among influenza subtypes in vaccines, so type A (H3N2) viruses are more likely to acquire mutations that help them escape the vaccine. Influenza A virus (H3N2) also appears to be more susceptible to changes in the path of adaptation to the egg environment. These factors may explain why influenza vaccines are less protective, especially against H3N2.
Although most flu vaccines are made using eggs, not all are. Some of the viruses used in influenza vaccines (which are inactive viruses) grow in mammalian cells, and recombinant influenza vaccines do not require live virus samples at all.
For the recombinant vaccines, the scientists make a synthetic gene that encodes the HA protein, and then the protein is produced inside the baculoviruses, which naturally infect the insects.
Some studies have suggested that genetically engineered hemagglutinin provides better protection against viruses grown in eggs, but that this needs to be confirmed in further research, Schaffner said.
Many researchers are working on new and improved flu vaccines that provide more protection. And do not need to be updated every year. For example, researchers at Stanford University are working on a vaccine for the flu that targets its stem instead of hemagglutinin (a similar vaccine called Flu-v appeared promising in an early clinical trial).
While the hemagglutinin protein mutates continuously, part of the stem looks the same in different strains of the flu and does not change from year to year; Therefore, by targeting the stem instead of the HA protein, influenza vaccines can provide protection against multiple strains and do not require updating. “Such a vaccine covers virtually all aspects of the flu,” Schaffner said.
A team of researchers looking for a broad-spectrum flu vaccine is targeting a different protein on the surface of the flu virus called neuraminidase. Other groups have found specific parts of the prominent HA that appear to be the same among different subtypes of influenza.
According to a 2020 report in the journal PNAS, adding some immune-boosting supplements or components to general influenza vaccines can also help them recall both trained B cells and inexperienced B cells. Take action and expand the body’s immune response.
In addition to groups seeking to develop general influenza vaccines, several vaccine manufacturers, including the modern companies Pfizer and Pfizer, which developed the Covid 19 vaccine, are testing influenza vaccines based on the mRNA genetic molecule. When mRNA enters the body, it instructs cells to make influenza antigens and teaches the immune system how to detect viruses.
Compared to vaccines grown in eggs that take several months to produce, mRNA vaccines can be made very quickly and do not require live samples of the virus. Thus, in theory, the strains needed to make vaccines could be selected closer to the onset of the flu season. As a result, vaccines are likely to be more compatible with circulating strains.
But for now, despite their shortcomings, existing flu vaccines are the best option to protect yourself against the flu. According to Schaffner, the flu vaccine that enters your arm offers minimal relative protection, but refrigerated vaccines never prevent any disease.