The Evolution of Influenza: Predicting and Preventing Epidemics

by Kelsey Wooddell

Each year, experts from the Food and Drug Administration (FDA), World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and other institutions study virus samples collected from around the world in order to identify the influenza viruses that are most likely to cause illness during the upcoming flu season.  Vaccines cannot be manufactured in real time with enough supplies to go around, so scientists have to predict which strains are most likely to outbreak, and how they will evolve.  There are more than 100 national influenza centers in more than 100 countries that conduct year-round surveillance for influenza viruses and disease activity, and these centers then send viruses for additional analyses to the five WHO Collaborating Centers for Reference and Research on Influenza.  In varies between countries, but in the U.S. the FDA determines what viruses will be used in U.S.-licensed vaccines.

A three-component (trivalent) vaccine has been used since the early 1980’s in order to protect against each of the two three main groups of influenza (A,B, and C) circulating in humans.  Human influenza A and B viruses cause seasonal epidemics almost every winter in the U.S. and the most common are therefore protected by the vaccine, whereas type C infections cause a mild respiratory illness and are not thought to cause epidemics.  The emergence of a new and very different influenza virus can cause an influenza pandemic.  This occurred in 2009 with the outbreak of what is now called the “2009 H1N1”, a type of influenza A virus, which caused the first influenza pandemic in over 40 years.  As of June 2012, it is estimated that the virus killed between 151,700 and 575,400 people worldwide, with young people being hit unusually hard.

Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H), which has 17 subtypes, and the neuraminidase (N), which has 10 subtypes.  Currently, the two types of influenza subtypes circling the population are influenza A (H1N1) and influenza A (H3N2).  The 2009 H1N1, however, was very different from the regular human influenza A (H1N1), and has now replaced the H1N1 that was previously circulating in humans.

Vaccines are looked down upon by many people for fear that they will create a super-virus, one selectively created by vaccines to be super-infections and super-resistant.  If a vaccinated person becomes infected with the virus, the body mounts an immune response that was created when the vaccine previously introduced the virus so it could begin to formulate antibodies.  However, that pressure from the immune system can provoke the virus to mutate into a slightly different - and possibly more infectious - form.

One study from MIT reveals the mechanism behind this phenomenon to be antigenic drift and analyzed which amino acids that made up the viral protein were most likely to undergo mutation that improve the viruses’ ability to infect new hosts.  This knowledge could help vaccine designers produce vaccines that don’t induce an evolution of fitter viruses.

Influenza A virus is such an effective virus because it has the ability to evade antibodies specific for its attachment protein, the hemagglutinin (HA).  The antigenic drift is a result of accumulating several substitutions of the HA epitope, the part of the virus that the immune system recognizes.  This means that the immune system no longer recognizes the virus, and therefore the antibodies cannot fight it.  If no vaccines can be specifically formulated to target the specific amino acids that tend to acquire substitutions, there is another option to increase the effectiveness of the vaccine.

Antigenic drift, according to the same study, can be mitigated most effectively by decreasing the number of passages of the influenza A virus between immune and nonimmune individuals, which in humans essentially means children.  Therefore, increasing the number of pediatric influenza A vaccination rates would likely slow antigenic drift and temporally extend the effectiveness of influenza vaccines.  Additionally, monitoring the most commonly mutating amino acids may assist in accurately predicting the strains of the influenza A virus with the greatest epidemic potential.

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Sources:

“CDC - Seasonal Influenza (Flu) - First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration.” Web. 3 Mar. 2013.

“CDC - Seasonal Influenza (Flu) - Types of Influenza Viruses.” Web. 3 Mar. 2013.

“CDC - Seasonal Influenza (Flu) - Vaccine Virus Selection for the 2012-2013 Influenza Season.” Web. 3 Mar. 2013.

Hensley, Scott E. et al. “Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift.” Science 326.5953 (2009): 734–736. Web. 3 Mar. 2013.

“Stopping Influenza Evolution Before It Starts - MIT News Office.” MIT’s News Office. Web. 3 Mar. 2013.