Flu vaccination mismatch in the 2015 flu season – What are the lessons learned?


Influenza, or the ‘flu’, is a serious illness that can lead to hospitalization and sometimes even death. Flu vaccinations are thought to be the best way to protect ourselves against catching and spreading the flu. However, this was not the case in 2015.

Influenza, otherwise known as the flu, is a severe infectious disease caused by the influenza virus. The flu can affect anyone and everyone, and in most cases only causes mild symptoms that go away after a couple of weeks. However, in ‘high risk’ individuals, particularly in children under 5 or adults above 65 years old, pregnant women and immunocompromised people or people with chronic health problems such as asthma, flu symptoms can be severe, requiring hospitalization and on occasion leading to death.  In fact, the Centers for Disease Control and Prevention (CDC) estimate that between 1976 and 2007 influenza accounted for 3.000-49.000 deaths every year, and about 95% of these deaths were among people older than 65.

What can we do to protect ourselves against this potentially dangerous virus?

Acquiring and maintaining some good personal hygiene habits for one, like frequent hand-washing, reduces the chances of getting infected. For individuals that are more susceptible to contracting the flu and suffering more severe symptoms, the World Health Organization (WHO) recommends yearly vaccinations against the influenza virus.

Since there exist many strains of the influenza virus, and every flu season is different, every year the WHO meets to select the virus strains that will comprise the vaccination for the coming year. This decision is based on data collected on factors, such as, which flu strains are circulating and how they are spreading.

The 2015 flu season was a bad one, with 266 out of 100.000 people over 65 years of age being hospitalized. This is the highest known rate so far, since recordings started in the 2005 flu season. One of the underlying causes for this was that the flu vaccine developed for the 2015 season was only 18% effective against the prevailing H3N3 influenza virus strain, leading to unsatisfactory protection of vaccinated risk groups.

What went wrong in the 2015 flu season?

To understand what went wrong and what the underlying problems leading to reduced flu vaccine effectiveness were in 2015, one has to take a step back and look at the lengthy process that precedes flu vaccine administration. In February, preceding a flu season (October to May), the WHO meets and analyzes data from more than 112 countries and announces its strain selection for the upcoming flu season. Then, a US Food and Drug Administration (FDA) advisory panel meets in March to approve these sections and kick off a time consuming process of producing millions of vaccine doses.  Thus, the process of predicting and selecting the relevant strains for a flu season takes place months before it actually starts.

Signs of trouble already appeared just weeks after the selection was made for the 2015 flu season. Tests showed that the circulating H3N2 strains had small but significant mutations on surface proteins that affect whether the body’s immune system can recognize the virus. The drifted strain began to predominate and caused more than 50% of the influenza cases in the last flu season. The vaccine developed earlier proved to be ineffective against the mutated H3N2 strains.

What are the lessons learned?

At this year’s March FDA meeting, concerns were raised to delay the approval of the strains to prevent future mismatches. Some voices even went as far as saying that the choice is rather “a game of chance and probability”. Choosing the right strains is also fundamental in maintaining public trust in vaccines. Experts like Andrew Pavia say that moving the strain selection by four months would allow for a consistently good match. But this would create severe problems with manufacturing the vaccines on time. This problem is based in the continued reliance on old manufacturing methods that rely on growing seed strains in chicken eggs, a method licensed in 1945. Other methods like recombinant versions of inactive viruses that are produced without eggs are much faster but rarely used in practice. Even these new methods are facing the roadblock of virus replication, which is a time consuming process.  Another major roadblock in the production of flu vaccines is the potency testing to determine the doses required to produce adequate immunity. Each strain requires a new potency test reagent.

With all these problems associated with manufacturing and the slow process in improving the speed of vaccine production, the focus shifts back to better prediction models. The CDC has improved its surveillance and methods of analyzing strains and the WHO held 3 international meetings to improve strain selection. New technologies, such as the development of synthetic viruses that could be used as vaccines, and technologies predicting the impact of strain mutations on the protective effect of existing vaccines need to be implemented to improve the process and prevent the latest mismatch from happening again.

The nature of influenza viruses and their capability to mutate cannot be changed. Thus, it will require maximum effort from all parties involved, including strain prediction and vaccine manufacturing, to stay on top of flu vaccination.



Cohen Marill, M. Nature Medicine 21, 297–298 (2015)

Tharakaraman, K. & Sasisekharan, R. Cell Host Microbe 17, 279-282 (2015)



Article last time updated on 05.05.2015.

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