Now, the big question is how we are going to do that?
One way is by understanding the structural characteristic of human immune system. That is, at least now I understand why it is important to understand the very detail of anatomy and function of antibodies. So, let me step into the detail of it by put what we have learned so far from our class into the context of influenza case.
So far, we have learn that antibody have hypervariable region called Vl (for the light chain) and Vh (for the heavy chain). There are also CDR (Complementary Determining Region) which determine the specificity of each antibody to antigen. We believe also that the antibody have million preexisting “types” to anticipate whatever kind of pathogen molecular structures. But perhaps that won’t works for influenza viruses?
There are 16 antigenically different HA subtypes and 9 antigenically different NA subtypes of influenza viruses. The combination of these two components define all known existing subtypes of Influenza A viruses.
Now, the problem is how our antibody system could provide a rather broad strain protection, than only targeting the HA surface antigen of the viruses, which capable for changing rapidly to avoid and escape from our immune system.
One way to study how our immune system can protect us is to study the how antibody that the survivor of a novel influenza infected person works on preventing from fatal condition.
There is a clue that the antibody of the survivor have a broad protection of flu viruses which might involve a specific region HA2 which is located at the stem or stalk of the HA protein, not at the head!. The HA1 region at the head is believe as a decoy for influenza viruses to escape from neutralization. So, it is suggested that vaccine developer should re-focus on Broad Neutralizing Antibodies (BnAb) that targeting hydrophobic stem region of HA2 and inhibit fusion process, which showed to be cross reactive for multiple viruses, rather then focus on antibody that works on HA1 epitopes. Do you believe that?
Reference:
Han, T. and W. A. Marasco "Structural basis of influenza virus neutralization." Ann N Y Acad Sci. 2011 Jan, 1217: 178-90.
View here.
If this region is conserved, the Ab your body makes from the vaccine should be able to target a broader array of flu strains and could keep you immunized for a longer time. However, this is a hydrophobic region, so it would not be naturally found on the exposed surface of the virus. If there are enough of these proteins around the virus you could imagine how difficult it would be for Ab to get in between and be able to bind to one of them. I predict that viruses will adapt to these vaccinations by gaining more of these proteins on their surface through evolution. The more proteins they have, the less Ab can bind to the constant regions, and the more likely they will be able to infect somebody and replicate.
ReplyDeleteFLU SHOT PROGRESS
ReplyDeleteAs flu season is full in swing, I am listening to tons of arguments on whether the flu shot is worth getting or not. Many people are aware of how fast the influenza virus changes and that the current vaccination is made from last season’s virus. This makes people think that it won’t help their immune system fight off the current flu going around and provide them with no useful protection. This is why so many people refuse to get vaccinated and go through the quick pinch of needle pain. How close are we to a universal influenza vaccine so we do not have to get one seasonally?
Apparently the world is possibly only a few years away! This is a very exciting area of research because of how much of the world it impacts and the economic importance of one universal vaccine. It is also difficult and expensive to make and distribute a global dispatch of the vaccine out to large populations of people.
Do you know how many deaths are caused by influenza in the United States alone? Admittedly this is hard to determine because of variable seasons and reporting inaccuracies, but the numbers are still astounding. The number of estimated deaths can range from 3,000 to 49,000 deaths in a high season! That surprised me!
Currently the seasonal vaccine depends on circulating an antibody directed the head of the major surface protein, HA and a second surface protein, NA. Some of these new vaccines being tested are focused on a newly discovered antibody in one patient, F16, which has been found to be incredibly versatile in that it has been proven to fend off many strains of influenza viruses. This is hopefully what will lead to a broader targeting vaccination that can be administered much longer than the current annual rate. Everything is in early testing phases still, but hope is here!
http://www.theasm.org.au/uploads/pdf/MICRO%20march%202011-8.pdf#page=36
http://www.futuremedicine.com/doi/abs/10.2217/fvl.10.80?journalCode=fvl
http://healthland.time.com/2011/07/29/researchers-say-a-universal-flu-vaccine-may-be-close-at-hand/
http://www.cdc.gov/flu/about/disease/us_flu-related_deaths.htm#how-many-die