The History and Shortcomings of the Influenza Vaccine

The summer of 1918 marked the beginning of the deadliest viral pandemic that the world has ever seen. The disease, which supposedly started in the barracks of soldiers waiting to go off to fight in World War I, spread quickly, leaving a trail of devastation in its wake. In a single year, it had sickened over a third of the world’s population and killed an estimated 50 million people (Byerly).

The disease responsible for all this destruction was a new strain of influenza that people at the time called Spanish Influenza or The Purple Death. As people became sick and died at frightening rates, doctors were unable to respond. They didn’t know what caused the flu, how it spread, or how to make medicine to treat it.

After that deadly summer, much more work went into trying to understand and treat the flu. With the help of a newly created process called ultrafiltration, influenza was identified as a virus in 1933 and then a vaccine for it was soon created by Soviet scientists(Smith and Anderewes) (Smorodintseff).

This new vaccine held the promise of protecting people from the debilitating and deadly flu, but unlike the yellow fever or smallpox vaccines, this immunization’s efficacy did not last long.

In just four years, the shot was deemed no longer effective. While trying to figure out why, researchers Thomas Francis and Jonas Salk (who is more famous for his work on the polio vaccine) discovered that the flu, unlike smallpox, consists of different strains of which the original shot only protected against one.

The US Army, in an effort to avoid another pandemic (soldiers were especially vulnerable during the 1918 outbreak due to close living quarters), funded Francis and Salk to develop a vaccine to protect people against the two strains, influenza A and B, of flu that their research had uncovered (Panltheier).

In this vaccine, Salk and Francis did not just have to making a single effective vaccine, but enough of the vaccine to vaccinate the entire US army. Their solution was to use chicken eggs to grow large amounts of the vaccine: a process we still model today.

In this process, workers first inject influenza virus into chicken eggs. Once inside, the cells multiply exponentially. Then the researchers open up the eggs, harvest the viral cells, and use chemicals to inactivate the viruses. That dead virus solution is what people then receive as the flu shot(CDC).

When that vaccine of inactivated virus enters a person’s body, their immune system identifies it as a foreign invader and then their immune system works to create B cells that create antibodies to the virus. Some of these B cells are saved as memory B cell and are able to recognize the vaccine’s that specific viral strain and mount an immune response if the person is ever exposed to that virus again.

Many viruses only exist in a single conformer or the antibodies a person creates can recognize all the types of that disease, so a vaccine can provide long term protection to the disease.

The the influenza virus, however has adapted to change its genetics constantly processes called genetic shift and drift, creating genetically unique hemagglutinin and neuraminidase transposons (envelope proteins) whose genetic differences trick the immune system into not recognizing these slightly genetically different virus as the same disease.

Marta Terra, a virologist at Stanford describes these coat proteins as different hats that the virus wears. When one strain of the flu enters the body wearing a red hat, the body’s immune immune system creates antibodies to recognize the red hat protein as a foreign invader. These antibodies will destroy the red hat viruses if they come back, but if the flu adapts to wear a different “hat” then it can sneak past these antibodies and infect cells undetected (Terre)’’

Because of the flu’s adaptability, the vaccine Francis and Salk made in 1944 only protected people from getting sick for a couple of years. By 1947 the vaccine provided “no evidence of a protective effect” from the flu (Francis).

That vaccine though wasn’t changed until 1957 (Parsonett). In 1957, a new flu virus a novel and especially deadly variant began to spread. As the new strain spread around the globe, researchers from the World Health Organization’s newly created Global Influenza Surveillance and Response System (GISRS) rushed to understand the outbreak and work with pharmaceutical companies to create a new vaccine, but the damage was already done (Encyclopedia Britanica). Two million people died of the flu that year (Jackson).

This same reactionary cycle continued for the next two decades, with new vaccines being released only after especially deadly flu outbreaks. These outbreaks generally occurred when the most prevelant flu strain’s genome shifted significantly and a new variant was born (Viboud).

The World Health Organization created a new policy in 1973 to go on the offensive in the fight against the flu. Starting that year, the WHO and CDC held annual meetings to discuss which strains of flu were emerging or circulating at that time. The panel then then gave recommendations to vaccine companies like Sanofi Pasture and Sequris of the three strains of flu they think would be most prevalent the next flu season(“Achievements in Public Health”)

Today, The CDC and WHO still track the spread of different strains of flu in people, pigs and poultry. They now meet biannually to determine the composition of the northern hemisphere and southern hemisphere flu shots for the next year. (Parsonett).

These efforts have helped preemptively protect people from flu, but around the world, the flu still sickens an average of 35 million people and kills between 300,000–500,000 people per year (CDC).

The arcane pre WWII method of flu vaccine manufacturing that we still use today has also led to some of the shortcomings in our fight to beat influenza. Flu vaccine production uses millions of eggs per year to grow the 3 different strains of the virus included in each year’s shot(Braur). Companies need at least six months to conduct this process before enough vaccines are ready for distribution (Pillar). Because of this, the CDC and WHO must make their recommendations for which strains to include in a shot that will come out in October by February. The time delay means that these recommendations are simply a guess at what will be most common variant 6 months from then. (Hannoun)

Using eggs to create vaccines is also a very labor intensive process which limits the number of strains that can included in the shot. Every year there are many different strains of flu circulating the globe, but these researchers must the hard choice of which three or four of those to put in the shot (Parsonett 2017).

Usually the CDC and WHO guess correctly and the vaccine created covers the most common strains of flu for that season, but in other years, like 2014, a new variation of a flu stain emerges during the gap of time between recommendation and distribution, rendering the flu shot for that year ineffective.

Yet another problem with the current process is that some strains of flu just do not grow well in eggs. So in some years, strains are chosen for a shot because of what can be grown and not because of what strains exist.

Lastly, even when the shot does contain the most common strains of flu, It is just not that effective of a vaccine. For example, this year’s shot contains the most common variants of the flu, but it is only 48% effective in preventing sickness among adults (CDC).

There is still much debate within the scientific community as to why in even a good year the vaccine only protects half the people that get it, but differences in a person’s genetics, changes to the immune system, and slight viral adaptations have all been discussed as possible factors (Anders-Terre)(Dusheck).

Right now our methods for creating flu vaccines really are based just based upon educated guesses. Every day we live in the possibility of a pandemic. The strain of flu that caused the 1918 pandemic can’t even be grow in chicken eggs, so none of us have been vaccinated to that deadly strain(NPR).

At any moment a new, virulent strain like that could emerge and cause unimaginable suffering and millions of deaths.

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