Flu Vaccine: The End of Gambling with Nature?

Flu Vaccine: The End of Gambling with Nature?

By Siwei Zhang

With the last bit of thunderstorm warning retreats into Lake Michigan, the hot and humid mist that once stretched from Willis Tower to Hancock Center dissipates – the summer time in Chicagoland is coming to an end and its renowned harsh winter is approaching quickly. As usual, local pharmacies, such as CVS and Walgreens, begin to prepare their autumn advertisement campaign on flu vaccines. Within a few weeks, large billboards bearing the sign of flu vaccination will be on display in stores, and people will begin to queue up for a flu vaccine, with the hope of giving their immune system a boost for the incoming winter against influenza.

It may sound slightly ridiculous for the layperson; however the development of flu vaccines every year is just a little bit better than a gamble – of course, with scientific methods, references, and data to assist decision-making processes. Since there are more than a thousand different flu virus strains currently in transmission and all of them continuously mutate and evolve, one vaccine surely cannot be a turn-key solution. Instead, as a classic example of epidemiology, pharmaceutical companies develop flu vaccines in a yearly-specific pattern, by using large data and previous records to predict the strain(s) that has/have the highest potential to infect the largest population. For example, data survey on prevalent flu strains in the southern hemisphere provides important reference to predict which strain(s) may hit the northern hemisphere in the next 6 months. Nevertheless, just like weather forecasts, the viral guesswork never works 100%, which leads to either a low protection ratio or, at its worst, no protection for the winter at all. To add more complexities into this topic, just remember the flu virus strains will continue to mutate and evolve throughout the winter, and new strains are being discovered at the rate of approximately 1 strain per week.

A flu vaccine relies on stimulating the immune system using specific pieces of a denatured virus, called immunogen, to produce antibodies before an actual infection occurs. Should an actual infection occur, the immune system will recognize the virus and produce large amounts of antibodies to neutralize the threat. However, as mentioned above, the immunogen only comes from one or a limited number of flu strains, and here is where the guesswork and gambling begins.

Two recent articles that appeared in Nature Medicine and Science address this problem using a different approach. Both researches focus on hemagglutinin (HA), a protein that forms part of the outer surface of the H1N1 strain (it is worth mentioning that part of the sequence derived from this protein, HA tag, has been widely used as an epitope tag in molecular biology). The protein is made of a head region, which is variable and a stem region, which is significantly conserved across different strains. Both researches applied special measurements to use the conserved stem region as an immunogen to produce flu vaccines that will react with a much wider range of flu strains, and the results obtained from initial animal experiments are promising. Currently, both projects are still at their research stage, and a potential industrial integration and further R&D activities are expected to be not only highly rewarding, but will also revolutionize the whole flu vaccine industry by putting an end to the gambling era.


Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015 Aug 24. doi: 10.1038/nm.3927.

A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015 Aug 24. pii: aac7263

Image courtesy of pixabay.com

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