According to the World Health Organization, seasonal influenza is a highly contagious viral infection that can affect anyone worldwide. However, influenza is not equally dangerous to all demographics. Influenza poses the greatest risks to children under two years, adults over 65, and people with certain medical conditions. CDC statistics show that in 2013 alone, 3,697 Americans died of influenza despite millions of Americans receiving the vaccine. Even with a vaccine, every year there are about five million cases of severe illness and between 250,000 to 500,000 deaths globally. This may not compare to more deadly diseases, however this number is still far too high for an illness we combatted pharmaceutically for nearly 60 years.   Clearly more needs to be done to prevent this disease; however, there are many hurdles to combating this virus.

     Influenza is caused by the influenza virus, and is characterized by a plethora of symptoms including sore throat, high fever, runny nose, headache, coughing, muscle/joint pain, and overall exhaustion. The virus can be classified as an A, B, or C virus and from there can be further divided into many different subtypes. For the purposes of this article, the subtypes that are most heavily investigated are the H1 and H3 subtypes of influenza A, and influenza B viruses. These subtypes receive the greatest attention because these are the strains that cause the epidemic infections in humans. These subtypes are important because their different features make treating influenza as a whole very difficult. Despite all that is known about the virus, the current vaccine cannot effectively target all of these subtypes equally effectively.

     Our current vaccine against influenza is the most effective preventative measure against influenza and has been on the market for 60 years. However, the vaccine falls short in key areas. While the vaccine has been shown to provide adequate protection for healthy adults, it does not efficiently protect the elderly, children, or individuals with compromised immune systems.  Instead, the vaccine only to limits the severity of the infection in these groups. Moreover, the current vaccine cannot prevent all cases of influenza due to the quick evolution of the virus. The current vaccine only targets three common strains of the virus which are assumed to be the most likely to circulate that year. These targeted types include two very specific strains of A viruses, and one B virus. To compound the problem, current vaccines are produced using an older technique where large quantities of the influenza viruses are passed into eggs and then split using detergents. The disadvantage of this technique is that it takes several months to produce a vaccine. Therefore, vaccine production  can lag behind any strain that is currently affecting the population. Vaccine production also relies on eggs, which means it cannot be given to those with egg related allergies, and cannot be used to fight many forms of the bird flu because many avian influenza viruses are egg-lethal. Despite all these problems in vaccine production, the most damaging features of our current vaccine is related to its target site.

These older vaccines work by binding to a surface glycoprotein that helps the virus bind to, and enter host cells. Unfortunately, the part of the glycoprotein that is targeted varies greatly between different strains. Therefore when the vaccine prevents one strain, others that it doesn’t target will spread more rapidly. Moreover, it is not possible to perfectly predict which new influenza strain will circulate in the future, and when the vaccine does not match the virus, both the numbers of infection and numbers of fatalities increase.

     The clear limitation with our current vaccine has provided many researchers with the goal of producing a universal influenza vaccine. One promising new strategy focuses on targeting the M2 protein in Influenza B viruses, which is responsible for uncoating the virus after entry into a cell. The advantage of this technique is that this protein is highly conserved and therefore a vaccine targeting it will have very broad effects over many strains of influenza. Its main disadvantage is that due to a structural difference between M2 proteins in Influenza A and B, the vaccine will only combat influenza B strains. While this may seem like a huge disadvantage, there are still massive advantages to this vaccine.

A new vaccine capable of better targeting influenza B strains would still be incredibly valuable because most years when a vaccine is mismatched to a virus, it is due to the unpredictability of the Influenza B virus. Currently the “traditional” vaccine is a trivalent vaccine, which means it targets for three strains of a particular virus. For influenza, two of these strains belong to the A type and one to the B type. Because only one B strain is targeted, often it is a different B strain that is missed by our vaccine and damages the population. A short term solution to this problem is to develop vaccines using our current method that targets four different strains instead of the usually three. If this fourth strain were an extra B virus, than our current vaccine may be more effective most years on matching its ever-changing target. Recently many locations are phasing out the trivalent vaccine, and replacing it with a quadrivalent one. While this process is proceeding slowly, it is clear that in a few years, the only available flu vaccine will be a quadrivalent one. Replacing the trivalent vaccine with a quadrivalent one and producing a new vaccine that better targets Type B viruses will broaden the influenza vaccine and increase the chance of success.

     Another new area of development aimed as a universal solution is a vaccine which would target different glycoproteins on the virus. The current vaccine binds to a region of the glycoprotein that is not highly conserved; slightly different strains may have a different sequence at this point. Thus, targeting a more conserved region will broaden the effectiveness of any possible vaccine. While results have varied depending on which domains were focussed on, it is clear that this could be a promising solution. Recent clinical trials have even proven it was safe to use on humans and neutralized some of subtypes of influenza. While there is still massive room for improvement, this will undoubtedly be the focus of heavy research for the foreseeable future.

     Many other lesser studied solutions also exist. One promising vaccine is designed to stimulate T cell immunity, strengthening the body’s own natural reaction to the disease. Although this is promising, far more work is needed to test its feasibility. However groups of scientists are researching all of these possibilities and many more in the hopes that they can finally find a more effective vaccine to protect us from a virus that still claims thousands of lives a year.

 

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REFERENCES

Influenza. (2015, July 17). Retrieved August 15, 2015, from http://www.cdc.gov/nchs/fastats/flu.htm]

Influenza. (n.d.). Retrieved August 13, 2015, from https://en.wikipedia.org/wiki/Influenza

“Influenza (Seasonal) Fact sheet N°211”. (2014, March) Retrieved August 15, 2015.

Pica, N., & Palese, P. (2013). Toward a Universal Influenza Virus Vaccine: Prospects and Challenges. Annual Review of Medicine Annu. Rev. Med., 189-202. Retrieved August 16, 2015.

 

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