Flu Shots- To Vaccinate or Not to Vaccinate?

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According to the experts, the best way to prepare for the flu season is with a flu shot. In my adult years, I have never gotten a flu vaccine. I tell myself that this has been an educated decision from back when I took virology in graduate school. Seeing as that was years ago and I have had the flu once in my adult life I thought I’d brush up on the educated part of my decision. One thing that is in the negative column for getting the flu vaccination is there are different types, subtypes, and strains of influenza. The efficiency of a flu vaccine is an interplay between how many different strains are represented in the cocktail and how effective the exposure will be. Right now the magic number is three strains, and the Center for Disease Control (CDC) posts the recommendations as to which three strains should be included in a given year’s vaccination. This means that out of all the possible strains that are capable of infecting, the vaccine only protects against three of them in a given flu season.

The World Health Organization (WHO) makes its best guess as to which three strains are going to be the most problematic for the upcoming flu season. Most years this is a successful guess, but there are years when the three in the vaccine do not represent those which most infect people over that particular season. 2003 stands out as a mismatch year for example, where the most prevalent strains were not represented in the cocktail. According to the CDC website, the flu shot for the 2011-2012 season is the same cocktail of three flu viruses which the shot contained for the 2010-2011 season. Even so it is still recommended everyone, including those who got the vaccine last year, get vaccinated. Let’s backtrack a little here in order to look closer at the virus and how the naming of the strains occurs.

Influenza virus is a negative-sense, single strand RNA virus belonging to the Orthomyxovirus family. A negative-sense RNA virus needs to have in its genome coding to make its own RNA polymerase in order to make the copy that passes as mRNA in the host. A positive-sense stranded RNA virus is already oriented in the same way as host mRNA and does not need an RNA polymerase to make the complementary strand. The mutation rate in RNA viruses compared to DNA viruses is higher due to the error rate of RNA polymerase. Another key factor is the organization of the viral genome- for influenza the genome is segmented. This means the RNA is divided into separate sections and it is all contained within a single virus particle. The mutation rate and the segmented nature of the genome are key factors in the effectiveness of the influenza virus, to be touched upon later. Influenza‘s genome is made up of only eight genes. Four genes make up the components necessary for transcription- PA, PB1, and PB2-which work along with the nucleoprotein made by the NP gene. The M gene makes up two matrix proteins and the NS gene codes for two non-structural proteins. These genes are both able to make two different products due to a shift in the reading frame. Lastly, The HA gene codes for the surface protein haemagglutinin (or hemagglutinin), while the NA gene codes for a second surface protein neuraminidase.

There are three types of Influenza A, B, and C this nomenclature goes in order of severity of infection. A is the type that almost all outbreaks are caused by, B causes a milder infection than A, and C doesn’t really cause much infection at all. The nucleoprotein varies for each of the three types. Since the 2009 flu outbreak, most people are familiar with the phrase H1N1. This additional naming of the flu virus is the subtype and it is only used for type A. H refers to the hemagglutinin protein and N refers to neuraminidase protein. Hemagglutinin and neuraminidase are responsible for the virus binding to host cells; this binding is the first step to the virus causing the host harm. The last part of naming is strain, and this is used only for type A and B. For example in 2011 the strains included in the vaccine were ‘A/California/7/2009 (H1N1)-like virus, ‘A/Perth/16/2009 (H3N2)-like virus’ and ‘B/Brisbane/60/2008-like virus.’ The origin of the virus, the laboratory that identified it, and the year of the outbreak are also included in the full naming along with the type and subtype. Another common feature found in the naming of flu viruses is the organism that particular strain infects.

The hemagglutinin is known to have 16 subtypes, while the neuraminidase has 9 known subtypes. H1, H2, and H3 are those known to infect human while N1 and N2 are the two out of nine neuraminidase subtypes which infect humans. The other subtypes for these proteins are found to infect other species such as birds and pigs. The species specificity boils down to these surface proteins- they are the key to entering the host cells but in order to get in the surface protein must identify and bind to a particular sugar reside on the host cell’s receptor. In theory the lack of a particular sugar residue on a given species’ receptor is the reason why only certain subtypes of the Influenza A are able to infect that particular species. However some of the characteristics of Influenza previously pointed out, namely the mutation tendencies, allow for inter-species infectivity. When two subtypes have the opportunity to intermingle, gene reassortment of the virus’ genes can occur and this creates a genetically novel flu strain. The venue for this gene reassortment is theorized to be a species which can be infected by various subtypes of the flu virus. This theory was looked into in an article in the Journal of Virology in 1999 by Zhou et al. The paper details this idea of two strains of virus, one human and one avian, infecting a third host simultaneously and rearranging to form new genetic variations of the virus. The host in recent years is pig, which is known to be infected by both human and avian strains of the flu. This reassortment allows for new versions of flu which the immune system has no experience fighting and are not represented in any flu vaccines for initial outbreaks.

Depiction of Influenza reassortment, author:   Lachlanfotheringham information from Neumann et al, 2009. Source: Wikimedia commons, GNU free documentation license.
Depiction of Influenza reassortment, author: Lachlanfotheringham information from Neumann et al, 2009. Source: Wikimedia commons, GNU free documentation license.

Flu Pandemics

Year
Strain
Origin
Estimated # of Deaths
1889-1890
H2N2 or H3N8
Spain
1 million
1918
H1N1
Spain
50-100 million
1957-58
H2N2
Asia
1-1.5 million
1967-68
H3N2
Hong Kong
1 million
2009
H1N1
Mexico
2500-6000
The Russian Flu or Red Flu was named for the supposed place of origin, although it was later attributed to starting in China. It is not included in the table as it was an epidemic affecting children and did not reach pandemic status.

Epidemic- fast spreading disease outbreak, exceeds normal expectations of number of people infected and/or spread of infection

Pandemic- a global epidemic

Endemic- when an infection is contained within the population/geographical location where it originated.


Research was conducted at MIT and data was released in the summer of 2013 on the possibility of H3N2 being the next big concern for humans. The reasoning makes sense, the original Flu pandemic in 1918 was H1N1 it then laid dormant in animals before striking humans again in 2009. Since human immune response is complex the immune system will lose the ability to fight off a dormant subtype because it is busy fighting off more active ones. Avian and swine flu evolve at a much slower rate than human versions so they have long forgotten subtypes for us still infecting their populations. Outbreaks can and have occurred when these animal forms find their way into humans and we are no longer prepared to fight them off. H3N2 struck in 1968 and could re-emerge as the next big flu outbreak. In an anticipatory effort the researchers at MIT looked specifically at the HA protein as the key to the viruses' infectivity, comparing 1100 current H3 strains to the infamous strain from 1968. About half of the ones studied could become a problem for humans which is scary enough but this is compounded with the evidence these researchers found that current H3 vaccines did not detect these strains in experiments.

There is a lot of information that can be learned about the flu virus, this is really just skimming the surface. Even though this brief glimpse makes the negative column stack up, the positives are there as well. Sure there is the realistic view of the cocktail vaccine being a best guess, the knowledge there are lots of other subtypes/strains not represented in the vaccine, and scarily new ones re-assorting themselves in unsuspecting pigs and re-emerging from both swine and avian populations. However, all of this still doesn’t add up to avoiding a vaccination that could very well prevent a person from being laid up in bed for several day feeling like they have been hit by a Mack truck. Even if the negatives outweigh the positives, the bottom line is there’s really no harm in going to any number of convenient places and getting a quick shot that could prevent the flu. But it is important to remember that flu shot or not no one is invincible. Good hygiene and common sense are key for making it through the flu season successfully.

Do you get the flu shot every year?

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