Every year, millions of people get vaccinated for the flu, yet the disease keeps coming back each season. The flu is a common condition caused by viruses called influenza. It is highly contagious and a recent study showed that simply breathing is enough to spread the viruses from an infected person. 

Vaccine or not, the flu affects millions of people yearly
The flu is a common condition caused by viruses called influenza

The flu affects 10% of the worldwide adult population and 25% of the children. The world’s poorest regions and elderly people are preferentially affected by the flu. The flu is normally not dangerous for healthy individuals, but in some rare cases, it can lead to death, as it could be the case for aged people, children or individuals with weakened immune systems or preexisting health problems. 

Researchers and health workers fight the flu and save many lives by creating new flu vaccines every year. However, the flu is not completely controlled in this way and it still leads to hospitalization and even death in severe cases. So, why is it we don’t have a better vaccine for influenza yet? And why do we need to get the shot every year? Wouldn’t it be easier to have a universal flu vaccine that we deliver once and is effective forever? Let’s try to answer these questions below! 

Why do we need another flu vaccine every year? 

Due to a number of reasons, scientists have not yet been able to develop the perfect, universal vaccine for the flu. The flu viruses have the nasty habit of changing their biological structure through a process known as mutation. The problem is that these viruses, with modified biologic structure, cannot be killed anymore by the old vaccination, so a new vaccine needs to be developed for the next season. 

A new vaccine needs to be developed for each flu season
A new vaccine needs to be developed for each flu season

Each year, epidemiologists and scientists conduct new studies to determine which types of flu viruses are likely to pervade in the current season. Based on research forecasts, scientists modify the vaccinations every year so that it can effectively combat the prevailing types of flu viruses in a given area or country. 

The performance of the flu vaccines varies widely from season to season. Several factors affect the effectiveness of the vaccines. Incorrect forecasts, sudden outburst of unanticipated flu viruses, and mutations of the viruses during the vaccine preparation process significantly impact the performance from year to year and from one age group to another. 

For the scientists engaged in the fight with the flu, the dream is to develop a robust universal influenza vaccine capable of providing long-lasting immunity against various subtypes of flu viruses.   

How does the flu vaccine work? 

Through vaccinations, inactive (very feeble or dead) flu viruses are delivered into our body. Their presence stimulates the immune system to activate the defense mechanisms that fight against the flu. In response to the presence of the viruses, the immune system starts to produce special proteins called antibodies that recognize specifically a particular type of flu viruses. When a vaccinated person contracts the flu, so the real viruses enter the body, the antibodies will recognize them, trigger an immune response and ultimately kill them. This is basically the ultimate purpose of the flu vaccination: to eliminate the viruses before the disease is triggered! 

The antibodies can only recognize a small region of the flu virus and this is determined by the way the vaccine was designed. Most vaccines target the head region of a molecule called hemagglutinin found in the viral particles. If the target structure is different between virus strains, the vaccine will not be equally effective against all virus types. In fact, it is still extremely difficult to stimulate the immune system to recognize and kill all flu viruses using the same vaccine, because of this variability in the structure.   

The antibodies generated after vaccination recognize the flu viruses, bind to them and trigger an immune defense reaction
The antibodies generated after vaccination recognize the flu viruses, bind to them and trigger an immune defense reaction

Types of influenza (flu) viruses 

Flu viruses are classified in different classes based on the proteins attached to their surface. Three types of viruses cause the flu in humans: A, B, and C. A fourth type, the D virus, causes influenza only in cattle. To make matters even worse, each type is further divided into several subtypes of viruses, called strains, each different from the others.

Type A is the most dangerous virus and the most difficult to target because it changes its structure regularly. It is the one responsible for spreading wide-scale flu pandemics because it can easily elude both our immune system and the influenza vaccination. The flu caused by type B viruses can range from severe to gentle. However, type C causes only mild flu. It doesn’t cause pandemics.

Typical structure of the influenza virus. Notice the hemagglutinin molecules (blue) on the surface of the virus, normally targeted by current vaccines
Typical structure of the influenza virus. Notice the hemagglutinin molecules (blue) on the surface of the virus, normally targeted by current vaccines

In order to be more efficient, vaccines are modified regularly based on information provided by international surveillance of the changes in the biological structure of flu viruses. Usually, the vaccines stimulate our immune system to fight against three or four subtypes of type A and type B viruses. These vaccines are known as trivalent and quadrivalent vaccines. They are ineffective against all other strains of influenza (for which the vaccine was not optimized).

There are also variants of these vaccinations for different age groups. The minimum age to get the flu vaccination is six months. Once injected, the flu vaccine usually requires two weeks to produce the necessary antibodies to fight the disease. An important observation is that flu vaccinations can sometimes trigger allergies; hence, patients should share their medical history with the physician before getting a shot of flu vaccine.

The concept of the universal flu vaccine 

Science has shown that most of the antibodies attack the head of the hemagglutinin molecules of the viruses. Although different types of flu viruses are different from each other, they share some similarities, especially in the structure of the hemagglutinin's stem. The hemagglutinin stem does not mutate (change), so targeting it could make the universal vaccine possible. Scientists are now trying to develop vaccines that can target common (conserved) physical regions from different types of viruses. If a vaccine can target a common region in the virus, it will be effective against all viruses containing that region, so it can be a true universal vaccine, fighting against multiple influenza strains. 

Some scientists are trying to make vaccines that trigger a stronger immune response from disease-fighting T blood cells (a type of cells from the immune system). These vaccinations aim to attack the flu virus at two stages: first through antibodies and later through the T blood cells. The more violent response from T blood cells can provide immunity for longer periods of time; hence, these vaccines could decrease the need to get the vaccine shot every year. 

Another approach for the universal flu vaccine involves developing special molecules known as immunogens, molecules that trigger an immune response. These molecules have a biological structure similar to some parts of the flu viruses. However, they are not viruses; rather they try to trick the body defense system to believe that the virus is present and initiate the fight against it. When immunogens are detected, our body generates a precise set of antibodies that will help to eliminate the flu viruses (once the real disease is contacted). Immunogenic molecules are used to produce immunity against the flu without being exposed to the original virus particles. Immunogenic molecules also have the potential to induce very precise immune responses, against the desired target region from a virus strain. Hence, immunogens have great potential to be used for the generation of a universal flu vaccine, and science is working already in this direction.    

Scientific advances in developing the universal flu vaccine 

The current methods used to develop the vaccine are sometimes less efficient than expected. In the 2017-2018 flu season, the available vaccine was only 38% effective in the United States. Scientists advocate for new technologies to be used for developing influenza vaccines.

One alternative could be represented by recombinant DNA technologies. This approach involves the isolation of a protein naturally found in flu viruses. Next, the protein is introduced into a new type of virus which can infect insect cells in the lab and can multiply in this way. Thus, a high quantity of viral protein can be produced and this protein will be included in the future flu vaccines.

Another direction of research aims to identify new targets inside the structure of the viruses for the vaccines. Scientists are now targeting regions of the virus that do not change over time. This will allow for a more efficient vaccine to be produced, effective against multiple types of flu viruses at the same time.

Governments, pharmaceutical companies, and scientists from all around the globe are interested in developing a universal flu vaccine. There are already clinical trials conducted to assess new types of vaccines, some of them coming pretty close to a universal flu vaccine. The National Institute of Allergic and Infectious diseases (USA) has published a strategic plan for developing a universal influenza vaccine. The aim is to create a vaccine that provides long-term protection for all ages, against multiple strains of flu viruses. It has established standards for universal vaccination. According to the Institute, a universal flu vaccine should be at least 75% effective for flu viruses of type A, and the vaccine should be suitable for all age groups and provide immunity for a minimum of one year.

Recent progress in the fields of virology and immunology has made scientists optimistic about creating the universal flu vaccine. Although it is hard to tell when this will become a reality, it is certain that these universal vaccines will reduce the frequency of vaccination, improve the protection against the flu and decrease the economic burden associated with the flu.

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