Why Flu Vaccines are Recommended Despite Low Efficacy

Every fall, any visit to a local doctor or pharmacy will likely prompt the question, “Did you get your flu vaccine yet?” While some get the jab faithfully each flu season, about half of the American population declines, likely over doubts of the vaccine’s effectiveness and necessity.  

While the childhood MMR vaccine touts real-world effectiveness at 97% for preventing measles, 88% effective against mumps, and 97% against rubella, the annual flu shot pales in comparison, coming in at somewhere around 40-60% effective. And that’s for a “good year,” where the viral strain predictions are closely match circulating strains. So, why can’t we come up with more effective flu vaccines? 

The heart of the problem is the influenza virus’ rapid mutation. If you’ve ever seen a quick-change artist perform, you’re amazed at how the artist can go from a floor-length ball gown to a short strappy dress in a matter of seconds. The feat seems nearly impossible.  

Scientists watch the influenza virus in its quick-change performance each year. By examining what strains are actively circulating in February, consultants from WHO-affiliated centers come up with their best guesses as to which strains are likely to be best-fitted for the upcoming winter in the Northern Hemisphere.  

Vanderbilt University infectious disease specialist Dr. William Shaffner explained, “You try to anticipate which strains are going to be active during your winter, early. But we have to project, because it takes time to make the vaccine.” 

Most of our current flu vaccines are quadrivalent, meaning, they train the immune system to fight four types of influenza virus: two influenza A viruses (H1N1 and H3N2) and two influenza B viruses.  

The genetic code mutations on these four most common strains change the proteins that appear on the virus’ outer surface. The flu shots train the body to recognize one of those surface proteins, hemagglutinin (HA).  

The coronavirus pandemic has cemented in our minds images of a virus with those spike proteins poking out like little trees on the surface. Likewise, the HA protein head, the canopy section of the tree that the vaccines trigger antibody responses too, enables the flu virus to bind to our cells to infiltrate and cause infection. But when the mutation causes a quick change of the appearance of that protein, the training becomes a moot point. The immune system can no longer recognize the protein and doesn’t mount the correct immune response.  

Sometimes the predictions from the WHO centers are accurate, resulting in that 40–60% effective shot. Other times the virus has mutated further by the time flu season hits, and the effectiveness drops even more. Research has suggested that the flu vaccine's effectiveness is also undermined by previous exposures, particularly during childhood.  

Most flu vaccines are made up of viruses grown in chicken eggs, which could also dampen the shot’s effectiveness. The vaccine virus may pick up its own mutations as it replicates, causing it to resemble the active flu strains less accurately.  

Multiple pharmaceutical companies are working on what they’re calling universal influenza vaccines. These formulations would provide long-lasting protection against numerous flu virus strains, including existing and emergent ones, thereby increasing effectiveness and hopefully eliminating the need for annual vaccination.  

The NIH is currently in a first-in-human trial, enrolling 40 healthy adult participants to study its universal vaccine candidate. The study is anticipated to be completed by 2023. 

Other companies are targeting the HA protein stalk, the trunk of the tree, as they have shown that portion of the protein to be less changing as the virus mutates. A new candidate being studied by a multi-institutional consortium funded by the U.S. National Insititute of Allergy and Infectious Diseases targets that stalk and has passed its first test in a small clinical trial. For the first time, the study proves a vaccine strategy producing stalk-reactive antibodies in humans is possible.  

Meanwhile, the COVID-19 VIP mRNA is also putting its hand to the plow to create an influenza vaccine. Moderna, Sanofi with Translate Bio, and Pfizer all have mRNA-powered seasonal flu vaccine candidates, which have moved into early-clinical testing with more companies hot on their heels. MRNA vaccines tend to cause more side effects, so safety is likely the biggest stumbling block for these candidates. However, the potential for a much more effective flu vaccine makes the concept worth exploring.  

Even with its less than stellar effective rates, the flu shot is still worth getting. According to a 2021 review published by vaccine, adults who were vaccinated against the flu and still got sick were 26% less likely to require intensive care. Vaccinated patients who ended up in the hospital were also 31% less likely to die from the flu. Data estimates that the vaccine prevented 7.5 million people from getting sick last flu season and prevented 6,300 flu-related deaths.  

The World Health Organization (WHO) estimates that the flu kills 290,000 to 650,000 people globally each year. Currently, our best defense is still an annual dose of the updated flu vaccine.