A Universal Flu Shot

Heading to the doctor’s office to get a flu shot may become a remnant of the past. Unlike vaccines for other viruses, the flu vaccine requires annual renewal to be effective. Researchers are aiming to change this paradigm by designing a universal vaccine that would be effective against most flu strains.

Caused by the influenza virus, the flu is a contagious disease that infects the nose, throat and lungs. The virus is transmitted through air droplets generated by coughing, sneezing or talking. Individuals nearby an infected person receive these droplets through the mouth or nose, allowing the virus to spread through the respiratory tract. Symptoms typically begin 1-4 days after exposure, but the period of contagiousness can extend on either side of that window, meaning an asymptomatic person can still transmit the virus to someone else. Flu symptoms generally come on suddenly and include fever, cough, sore throat, runny nose, body aches, headaches and fatigue.

A healthy person infected with influenza will generally experience a mild illness and will recover within two weeks without the help of medical care or antivirals. However, the flu can be a more serious illness for immunocompromised populations including the elderly, as well as young children, pregnant women and people with chronic conditions such as asthma or congestive heart failure. Since 2010, the CDC estimates that the flu has caused 9-35 million illnesses, 140,000-710,000 hospitalizations and 12,000-56,000 deaths annually. The best defense against the flu is a yearly vaccine, recommended for anyone over the age of 6 months.

Our immune systems recognize influenza from two of its surface proteins, hemagglutinin (H) and neuraminidase (N). These distinguishing features come in a variety pack – 18 different H subtypes and 11 different N subtypes – which can combine to generate different flu strains. The influenza virus mutates these proteins through antigenic drift and antigenic shift. Antigenic drift describes the small changes in the viral genome as the virus continually replicates. Because these mutations are minor, the new virus is genetically similar to the old virus. The human immune system can usually recognize closely related viruses and mount an appropriate response. However, over time these small changes add up to a virus that is very different than the original. In this case, the immune system cannot recognize the new virus and the response will take longer and can result in a more serious illness.

In contrast to drift, antigenic shift is a sudden, major change in the viral genome. Similar to changes accumulated over time with antigenic drift, antigenic shift will obstruct the immune response. Because the flu is a rapidly changing virus, the antibodies your body made from last year’s vaccine may not be effective against the strains going around this year.

Scientists currently design a new flu vaccine each year using epidemiological modeling and forecasting. With 100 national influenza centers around the world, researchers monitor which strains are circulating and predict what the next flu season will look like. In February of each year, the WHO and FDA decide which strains will go into the vaccine for the upcoming flu season. Sometimes the vaccine is very effective and other times the modeling does not accurately predict which strains will be prominent. In the latter case, the vaccine will not effectively protect even those who are immunized, resulting in a “bad” flu season.

Researchers are now determining the feasibility of a more universal influenza vaccine. The vaccines we use today target a region of the hemagglutinin protein, called the “head”, that frequently mutates. The head sits atop a “stalk” that is believed to stay relatively constant from one strain to the next. A vaccine that targets this region seems like it would provide broader protection across strains. A study published in Scientific Reports by scientists at the University of Rochester specifically examined the mutation rates in the stalk region compared to the head to understand how stable the stalk region would be under pressure from human antibodies. They exposed the H1N1 flu virus to antibodies and looked at changes in both regions of the hemagglutinin protein. Not surprisingly, they found many mutations in the head region and relatively few changes in the stalk region. The researchers point out that, while the mutation rates appear lower in the stalk region, there is still room for changes under immuno-selective pressure. In other words, the virus could eventually mutate and escape the protection offered by a universal vaccine.

This research is significant as it shows that we may never be able to have one influenza vaccine that lasts a lifetime, but the annual vaccine could become something we tell our grandchildren about. While we wait for a longer-lasting solution, there is still time to get a flu shot for this season!

Interested in studying the flu? Check out our available influenza antibodies, developed and made available by investigators at institutions such as the Icahn School of Medicine at Mount Sinai, University of Manitoba and New York Blood Center. Available targets include hemagglutinin, matrix protein, nucleoprotein, neuraminidase and non-structural protein 1.

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