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The 2017-2018 influenza season has been historically severe. Public health officials estimate that 900,000 Americans have been hospitalized and 80,000 have died of influenza and its complications. In comparison, the worst previous season of the last decade, 2010-2011, recorded 56,000 deaths. In a typical season, 30,000 Americans die.
So, why has the 2017-2018 season been such a bad year for the flu? There were two big factors.
First, one of the circulating influenza strains, A (H3N2), is particularly virulent and the vaccines that target it are less effective than those for other strains. In addition, most of the vaccines produced did not match the circulating subtype A (H3N2).
These problems reflect the particular biology of the influenza virus and vaccine production methods.
The flu virus is an artist who changes rapidly
Influenza is not a single static virus. There are three species – A, B and C – that can infect people. A is the most severe and C is rare, producing only mild symptoms. The flu is then divided into various subtypes and strains, depending on the viral properties.
Viruses are packets of proteins surrounding the viral genome, which in the influenza virus consists of RNA divided into eight distinct segments. The influenza virus is enveloped in a membrane layer derived from the host cell. Protein peaks, hemagglutinin (HA) and neuraminidase (NA), are required for the virus to cause the infection.
Your immune system responds to these two proteins first. Their properties determine the H and N designations of various viral strains – for example, the "swine flu" H1N1 that swept the world in 2009.
HA and NA proteins are constantly changing. The process of copying the genome of viral RNA is inherently chaotic. In addition, these two proteins are under strong pressure to evolve so as to escape the attacks of the immune system. This evolution of HA and NA proteins, called antigenic drift, prevents people from developing long-lasting immunity to the virus. Although the immune system may be ready to suppress strains already encountered, even slight changes may require the development of a completely new immune response before the infected person becomes resistant. Thus, we have epidemics of seasonal flu.
In addition, various subtypes of influenza A infect animals, the most important of them being domestic birds and pigs. If an animal is simultaneously infected with two different subtypes, the segments of their genomes can be scrambled together. Any resulting virus may have new properties, for which humans may have little or no immune defense. This process, called antigenic change, is responsible for the major pandemics that swept the world in the last century.
Prediction of influenza, production of a vaccine
In this context of antigenic change, the World Health Organization predicts each year what strains of influenza virus will circulate during the next influenza season, and vaccines are formulated from this information.
In 2017-2018, the vaccine was directed against specific subtypes of A (H1N1), A (H3N2) and B. The Centers for Disease Control and Prevention estimated that this vaccine was 40% effective for the prevention of the flu as a whole. But, significantly, it was only 25% effective against the particularly dangerous strain A (H3N2). This inadequacy probably reflects the way most vaccines are produced.
The usual way to produce an influenza vaccine begins with the growth of the virus in fertilized chicken eggs. After several days, the viruses are harvested, purified and inactivated, leaving the surface proteins, HA and NA, intact. However, when the virus is cultured in eggs, individual viruses with modifications of the HA protein increasing its ability to bind to chicken cells can grow better and become more common.
When people receive vaccines produced from these egg-adapted viruses, their immune systems learn to target egg-influenced HA proteins and may not react to the HA proteins of viruses actually circulating in humans. Thus, the virus used to produce a large portion of the 2017-2018 vaccine caused an immune response that did not fully protect against the circulating A (H3N2) virus in the population – although it may have mitigated the severity of the influenza.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Small improvements and a universal vaccine
Scientists are looking for a better way to protect the world's population from the flu.
Two new vaccines that do not use egg-developed viruses are currently available. The first, a vaccine made from viruses grown in mammalian cells, has shown in preliminary studies that it is only 20% effective against A (H3N2) compared to the vaccine produced from eggs. The other, a "recombinant" vaccine composed solely of HA proteins, is produced in insect cells and its efficacy is still being evaluated.
The ideal solution is a "universal" vaccine that would protect against all influenza viruses, regardless of the mutation and evolution of strains. An effort is based on the fact that the "stem" of the influenza HA protein is less variable than the "head" that interacts with the surface of the host cell; but vaccines made from a cocktail of "rods" of HA proteins have proved disappointing so far. A vaccine consisting of two internal virus proteins, M1 and NP, which are much less variable than the proteins exposed to the surface, is currently undergoing clinical trials, as is another vaccine consisting of an exclusive blend of pieces of viral proteins. These vaccines are designed to stimulate 'memory' immune cells that persist after an infection, possibly offering lasting immunity.
Will the 2018-2019 influenza season be so bad?
Based primarily on the recent influenza season in South America, the World Health Organization has recommended replacing the subtype A (H3N2) in the vaccine with a subtype that is more similar to the A (H3N2) virus. in circulation. They also recommended replacing subtype B with the one that appeared in the United States at the end of the 2017-2018 season and has become increasingly common elsewhere. The WHO predicted that the subtype A (H1N1) in circulation would be the same as last year and that no change was therefore necessary in this regard. Thus, although the same strains are likely to circulate, epidemiologists expect vaccines to provide better protection.
The CDC recommends that all people 6 months and older get the flu shot every year, but in general less than half of Americans do. Influenza and its complications can be life threatening, especially for the young, the elderly and the weak. In most years, the vaccine matches the circulating viral strain, and even a poorly matched vaccine provides protection. In addition, large-scale vaccination prevents the spread of the virus and protects vulnerable people.
The first flu-related death of the 2018-2019 season has already occurred – a healthy but unvaccinated child has died in Florida – claiming the importance of being vaccinated against the flu.
By Patricia L. Foster, Professor Emeritus of Biology at the University of Indiana
Photo by Jeff Chiu / Associated Press
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