T cells to the Rescue!

This looks like a job for the immune system!

Arggh!  November was hectic!  I haven’t abandoned you Omnimmune!  Sometimes getting a paper published takes precedence.  But I just came across this Time article with exciting news that Washington University scientists are closer to a vaccine to target breast cancer.  The original article was published at Clinical Cancer Research here, and once again highlights the power of the immune system!

This was a Phase I clinical trial to determine the safety of a vaccine targeting a protein called MAM-A.  The vaccine is a DNA vaccine that makes use of little circular bits of DNA that can be made in bacterial cells.  The bacteria are engineered so that they have the “DNA code” for MAM-A.  MAM-A is a protein that is specific to breast cancer as opposed to other cancers, and 40-80% of primary breast cancers make too much of it. Using bacteria allows for the production of lots of this DNA relatively easily.  An added benefit is that DNA from humans and bacteria look slightly different.  That means the immune system will see this DNA as foreign (danger! danger!)….basically it amps up your immune cells. When the vaccine is injected into a patient, cells (usually muscle) take up the DNA and make the protein (MAM-A).  Immune cells “eat” these proteins and present bits of MAM-A to T cells and B cells.  The T cells, particularly CD8+ T cells, then circulate throughout the body until they encounter breast cancer cells that make MAM-A. Because the CD8+ T cells have been “activated” (they’ve already been educated about the danger) they are able to kill those cancerous cells.

This study showed that the vaccine was safe to use.  But the most exciting part is that the vaccine caused CD8+ T cells specific to MAM-A to increase in number and to make the weapons needed to kill cancerous cells (one of those weapons being Interferon-γ).  They were in fact also able to kill cancerous cells, and patients receiving the vaccine had  improved “Progression Free Survival” compared to patients not receiving the vaccine.

This is a great example of cancer therapies taking advantage of the immune system!

Shoo Flu!

It’s October!  The start of my favorite season: trees turn to fire, crisp cool air makes hiking spectacular, and if you live in St. Louis the Cardinals are fighting to get to the World Series!

I mean that video is some infectious happiness  brought on by a game-winning home run!  But this is a very serious immunology blog so let’s get back to other infectious business. What else does October bring?  The start of flu season!  And therefore time to get the influenza vaccine!

The basis of the influenza vaccine is something called immunological memory…a fancy way of saying that cells of the immune system remember a virus they have seen before and are therefore able to get rid of it more effectively.  Cells of the adaptive immune system (B cells and T cells) are the cells responsible for this memory.  If you have an intruder one time (say into the White House), hopefully you take precautions to prevent it from happening again…like locking the door or keeping security guards nearby to tackle said intruder!  One way our immune system “locks the door” is by creating neutralizing antibodies.  Take a look at the picture of influenza below. The virus is coated in proteins.  Two are very important: hemmaglutinin (HA) and neuraminidase (NA).  HA allows the virus to attach to and gain entry into your cells.  Once inside the cell, influenza hijacks your cells and makes a whole bunch of new virus.  But all of these new viruses need to get out so that they can infect more cells. NA (in green) allow the virus to make its exit.

Influenza Virus–Note the Hemmaglutinin (HA in yellow) and Neuraminidase (NA in green).

“Not in my house!”

B cells make antibodies that bind to these proteins (especially HA) and therefore block their ability to get into your cells.  Certain types of B cells (memory B cells) are specialized to stick around for a long time after initial infection so that if you are reinfected with the same strain of influenza, lots of these antibodies can be made very quickly.  The influenza vaccines are designed to jump start these B cells.  If you’re infected at a later time during that season, the B cells will be ready to go.  Lots of antibodies will be made preventing the influenza virus from causing you too much sickness.

HA and NA are the basis for the naming system of different influenza strains.  The strains of virus that we are vaccinated with every fall are called H3N2 and H1N1.  These are the strains that cause seasonal influenza.  We’ve all been infected with these viruses, so why isn’t our “immunological memory” able to prevent reinfection? The answer is that influenza is very good at mutating (or changing) itself to avoid our immune response. Especially those HA and NA proteins that are on its surface, the ones we are able to make antibodies against.  In affect, influenza changes so that the antibodies that we make are no longer able to block infection or at least decrease their efficiency at doing so.  Every year, the World Health Organization, collects more than 500,000 samples from patients around the world who have influenza.  They then use these samples to make predictions about what next year’s strain of influenza will look like, particularly regarding HA.  Using this information, WHO is then able to guide production of the next year’s influenza vaccine.

Is it possible to create a vaccine that would be able to last for more than one season and against more strains of influenza?  Of course, scientists are attempting to do this.  If you look at the image above, you can see that HA kind of looks like a tree.  The big leafy parts of the “tree” are what mutates so easily in this virus.  The trunk of the virus stays pretty much the same regardless of strain, making it a good target for vaccines. Another target would be the M2 ion channel shown in the figure.  Like the trunks of HA, M2 doesn’t change too much from strain to strain.  Therefore, vaccines that generate antibodies to these different proteins would be effective against lots of different strains of virus from year to year.

We mostly think of influenza as a nuisance that makes us miss work occasionally.  But during the hysteria over the Ebola outbreak, we should also remember that influenza can be very deadly….50 million people died during the Spanish influenza epidemic in 1918.  More recently, the 2009 H1N1 pandemic caused 200,000 deaths within a year.

Go here for more information on the influenza vaccine.  This post was written with the help of this article.

And one more thing….poll time!