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By Dr. Anthony S. Fauci and Jennifer M. Routh

When it comes to infectious diseases, we must always be prepared for the unexpected. From the emergence of HIV/AIDS decades ago to the recent spread of Zika virus across the Americas, we continually see unknown diseases emerge and familiar diseases unpredictably re-emerge. Influenza, however, has remained a consistent threat for centuries.

As this year’s flu season winds down, manufacturers already are preparing updated vaccines for the upcoming flu season this fall and winter. While seasonal flu vaccines are important public health tools, our current approach can leave us one step behind the ever-changing influenza virus. Therefore, scientists at academic institutions, private companies and here at the National Institute of Allergy and Infectious Diseases (NIAID) are working to develop a universal influenza vaccine that would protect us against whatever flu strains that emerge.

Anyone who has caught the flu knows it can be a miserable experience. On a broader scale, seasonal influenza causes a substantial public health burden, and the potential for a new virus strain to emerge and cause a pandemic remains a likely possibility. Each year in the United States, seasonal influenza leads to between 140,000 and 710,000 hospitalizations and as many as 56,000 deaths.

The 2017-2018 U.S. influenza season has been particularly severe with high rates of hospitalizations and 156 influenza-associated pediatric deaths as of April 14, 2018. This year also marks the 100th anniversary of the 1918 influenza pandemic, during which one-third of the world’s population was infected with influenza and at least 50 million individuals died.

Despite substantial advances in science and medicine, we are still vulnerable to severe influenza seasons and devastating pandemics. Although it is always better to get the seasonal influenza vaccine than not, we must acknowledge the limitations of our current vaccines. Year after year, seasonal influenza vaccines have offered suboptimal protection, especially when compared to licensed vaccines for other infectious diseases.

Research shows that seasonal influenza vaccines are approximately 10 to 60 percent effective depending on the year. By contrast, two doses of the measles vaccine are approximately 97 percent effective, and do not require annual vaccination. In addition, seasonal influenza vaccines would offer virtually no protection against pandemic influenza strains.

A more protective and durable influenza vaccine has the potential to further reduce hospitalization rates and save thousands of lives annually. However, influenza poses unique scientific and logistical challenges. Influenza viruses constantly mutate, or drift, in small but important ways, which is why influenza vaccines are updated each year to best match the virus strains projected to circulate in the next season.

The cycle of updating the vaccine for the upcoming winter influenza season begins every February-March in the United States and requires a months-long manufacturing process that most commonly involves growing influenza viruses in eggs. By the time the U.S. influenza season begins in the late fall, mutated viruses can become more widespread than other circulating strains. Because the vaccine was not designed to protect against these mutated strains, it can be less effective.

The cycle of updating the vaccine for the upcoming winter influenza season begins every February-March in the United States and requires a months-long manufacturing process.

Research also suggests that the egg-based production process itself can lead to small changes in the vaccine virus that can contribute to low vaccine effectiveness. Other factors, such as a person’s age, their co-existing health conditions and their prior influenza exposures and vaccinations also impact how well influenza vaccines work.

Influenza viruses also can undergo more profound changes in composition at any time, resulting in a virus that is dramatically different from those that have circulated previously. Under such circumstances, few or no people would have immunity to the new form of the virus, leading to a pandemic. This scenario unfolded most recently in 2009 with the introduction of a new H1N1 influenza virus.

It is very likely that another influenza pandemic will occur eventually, although it is impossible to predict when it will happen and how severe it will be. As part of a larger preparedness effort for such an occurrence, the U.S. government develops and stockpiles vaccines against “pre-pandemic” influenza virus strains, animal viruses that occasionally infect humans, but do not yet spread efficiently among people.

There is a great deal of uncertainty to this approach since it is difficult to predict precisely which viruses may mutate to become easily transmittable. Also, like seasonal influenza viruses, these animal viruses may mutate after vaccines are produced, and new vaccines would need to be developed. This continually positions us one step behind the virus.

Not surprisingly, the limitations of seasonal influenza vaccines and the threat of an influenza pandemic have driven an extensive effort in the scientific community to develop a universal influenza vaccine — a vaccine that can provide durable protection for all age groups against multiple strains, including those that might cause a pandemic.

NIAID convened a workshop in June 2017 that gathered scientists from academia, industry and government to develop criteria for defining such a universal influenza vaccine, to identify knowledge gaps in influenza research, and to discuss strategies for addressing those gaps. Based on the deliberations of that meeting, NIAID recently issued a strategic plan to set a universal influenza vaccine research agenda.

Not surprisingly, the limitations of seasonal influenza vaccines and the threat of an influenza pandemic have driven an extensive effort to develop a universal vaccine.

One leading approach involves inducing an immune response against a part of the influenza virus that does not change from year to year. Although this may seem simple, it is actually a complicated effort because the immune system tends to respond to the part of the influenza virus that does change.

Advances in virology, immunology and vaccinology make this endeavor more feasible than it was a decade ago. However, scientists are still working to better understand how influenza transmits, what exactly makes certain infections more severe than others and how someone’s prior bouts of influenza or previous vaccinations could affect future infections, among other research questions

Overcoming these scientific challenges to create a universal vaccine will take time, but we believe it is possible. In the meantime, NIAID will continue to get our flu vaccine every year and encourage everyone to do the same. Some protection against influenza infection is better than none, and research shows that it can reduce your chances of severe illness and death if you do happen to catch this notorious virus.

Anthony S. Fauci, M.D., is director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. Jennifer M. Routh is an NIAID science writer/editor.