Did you get a flu shot this year? How about last year? In a world of next-day delivery and instant downloads, making the yearly pilgrimage to the doctor or the minute clinic feels like an outdated concept. Even if you get your shots free at the office, it’s still a pain to have to get vaccinated every year.
Unfortunately, there’s really no other way to deal with the annual threat of influenza. There’s no single vaccine for the flu because there are multiple strains that are always mutating. Unlike other viruses with one-and-done vaccinations, influenza is a moving target. Developing, producing, and distributing millions of vaccines every year is a massive operation that never stops, or even slows down a little bit. It’s basically Santa Claus territory — if Santa Claus delivered us all from mass epidemics.
The numbers are staggering. For the 2018-19 season, as in last year, there were 169.1 million doses distributed in the United States, up from 155.3 million doses the year before. How do they do it? We’re gonna roll up our sleeves and take a stab at it.
A Shot in the Dark
Although humans have endured seasonal misery for thousands of years, the first influenza virus was not identified until the 1930s. Before that, everyone thought influenza was caused by a strain of bacteria. The first influenza vaccine was created by Jonas Salk and Thomas Francis. Salk would use what he learned to eventually develop the polio vaccine in the early 1950s.
This beta-level flu shot protected against only one strain of influenza A. It was first used on soldiers in WWII before becoming available to the public. Since then, flu vaccines have evolved to target multiple strains of types A and B. These days, manufacturers are producing both trivalent vaccines, which cover two strains of influenza A and one strain of B, and quadrivalent vaccines that cover two strains of A and two strains of B.
A Race That Never Ends
Producing the modern flu vaccine is a year-round effort. As the flu season comes to an end in late February or early March, the World Health Organization, CDC, NIH, and FDA get together and develop a plan to tackle the upcoming season. They look at the strains from the season that just ended, and they look at what’s beginning to circulate in the southern hemisphere. From there, they try to predict what strains will show up in the coming fall.
Then they make recommendations to the private manufacturers who produce the vaccines about the strains they should cover. They also send candidate vaccine viruses to the manufacturers — seed viruses grown in chicken eggs — to get them started.
Finally, the manufacturers get to work creating their vaccines. They only have a few months to develop, test, and submit sample vaccines and test results to the FDA. Then the FDA does their own testing, and by late summer will begin to release lots back to the manufacturers. As soon as they are deemed okay, the manufacturers start shipping the shots.
You Gotta Break a Few Million Eggs
The oldest method for developing influenza vaccines involves fertilized chicken eggs. Each egg is tested to make sure it contains a viable embryo and is free from infection. The good eggs are washed, injected with flu virus, and left to incubate and multiply the viruses for four or five days. Then the viruses are extracted from the eggs, killed with heat, and loaded into syringes and vials.
Not everyone is tolerant of eggs or needles. Completely egg-free vaccines are produced using recombinant technology. The recombinant process isolates the hemagglutinin (HA) influenza virus gene and reproduces it inside insect cells with the help of another virus that excels at growing inside insect cells. When it’s time to package the vaccine, the HA protein is harvested from the cells and purified before packaging.
There is a third process known as the cell-based vaccine. In this method, viruses are grown inside of cultured cells from various mammals. Interestingly, this process was approved by the FDA for use starting in 2012, just one year before the recombinant process was approved. Up until the 2019-2020 flu season, cell-based vaccines were always the end result of cultures that originated as egg-grown vaccines. But this year marks the first completely egg-free, cell-based vaccine.
For the needle-shy, there is also a nasal mist version. This type of vaccine contains live but weakened flu virus strains, whereas the strains in the injected versions are completely inactive.
Walking on Eggshells
This annual race isn’t always a smooth run. One year there was an egg shortage because of avian flu. It’s no surprise that our vaccine production system is so dependent on eggs since there is a huge supply chain already in place. But the egg supply is always vulnerable to disruptions like the avian flu, and that’s one reason makers are trying to get away from egg-based manufacturing and move toward recombinant and other methods.
Logistically speaking, the vaccines require cold transport every step of the way, because influenza vaccines are quite susceptible to heat. You may find it of interest that there’s a whole cold chain required by the CDC (PDF) to keep the vaccines cold enough, but not frozen. It covers things like what type of cold storage devices to use, the location inside of those appliances that should be used for storage, and the type of hardware to use for temperature monitoring.
No matter how you take your vaccine, there is hope for a more infrequent dosing schedule. Researchers recently identified three new antibodies that bind to a different influenza virus protein known as neuraminidase (NA). These NA proteins change less frequently than HA proteins, so developing a vaccine that triggers the human body to defend against NA proteins instead could mean equal protection with less frequent vaccinations. Hey, it’s worth a shot.