Tuesday, February 10, 2015

So, what's in the measles vaccine anyways?

In the year 2000, measles was declared “eliminated” in the U.S. by the Centers for Disease Control.  But this was a short-lived victory for humanity.

As of 2001, measles appears to be making a comeback in the U.S., as illustrated nicely here by the U.S. Centers for Disease Control records.  It’s also happening in the UK.  As you may know, this resulted from clusters of people choosing to forgo the vaccination of their children.  Measles is highly contagious and still common in some parts of the world.

But in the developed world there is obviously some skepticism brewing regarding the safety of vaccines.  Much of this stems from a bogus study reported in 1998, which linked the measles-mumps-rubella (MMR) vaccine to autism.  This was discussed in great detail in an article that I previously posted in this blog.

Here in this article it is my intention to describe – in layman’s terms – exactly what is in an MMR vaccine.  I will focus specifically on the formulation used in a vaccine called M-M-R II®, which is manufactured by Merck.  Since 1978, over 575 million doses of this particular vaccine have been administered.  That makes it one of the most widely used vaccines for the measles virus, particularly in the U.S.

The full ingredient list for M-M-R II® can be found here.  And the precise amount of some of the ingredients per dose (0.5 milliliters) can be found here, along with just about anything else you would ever want to know about the safety of the vaccine according to the U.S. Food and Drug Administration (FDA).  The vaccine is supplied as a dehydrated (‘lyophilized’) powder because it can be easily shipped, stored, and held stable in that state for longer periods of time.  The powder is re-dissolved into sterile water immediately before the vaccine is administered by injection just below the skin, usually on the upper arm.

The purpose of any vaccine is to invoke an immune response to a harmless version of a virus so that you have antibodies to protect you from the real (harmful) version of the virus for the rest of your life.  In this context, a virus is also known as an ‘antigen’.  A vaccine virus can be made harmless – i.e. ‘attenuated’ – by removing genes or altering its biochemistry in some way that does not affect your body’s immune response to it. 

The M-M-R II® vaccine uses altered versions of the measles virus, the mumps virus, and the rubella (German measles) virus as active ingredients. 

Because viruses by nature cannot reproduce on their own, the vaccine viruses would need to be produced by growing a large number of cells from tissue contained in flasks (in a test-tube, so to speak).  The flasks contain a nutrient-rich liquid called cell culture growth medium.  Once cells are grown, they are then infected with a particular virus and then the virus will multiply and spread within the cells.  The gazillions of new viruses that are then produced from the infection are extracted and purified from the cells and the liquid growth medium. 

Here is a picture of one of my flasks from the lab, which contains a red cell culture growth medium.  I am sure Merck uses something a bit more sophisticated to meet their demands.

Ok, now on to the inactive ingredients.

You may be wondering: Doesn’t the vaccine also contain CHEMICALS?  Yes of course.  Everything in the universe is made out of chemicals, including you.  But are they harmful?  That is a much better question.

Let’s take a look.

1.       Sorbitol (C6H14O6), 0.0145 grams
Sorbitol is essentially a type of sugar.  Technically, it is also a type of alcohol.  It can be found naturally in various fruits.  It is also produced in the human body when excess glucose is broken down.  Because it tastes sweet and has a low glycemic index, it is often used in things like chewing gum and toothpaste.  Like most sugars, it can help stabilize biological material during dehydration and temperature changes.  For this purpose it is likely to be included in the vaccine.  Sorbitol can cause diarrhea if consumed in sufficient doses.  Incidentally, it can be found in some laxatives as well. 

2.       Sodium phosphate (Na+, H+, PO43-)
3.       Potassium phosphate (K+, H+, PO43-)
These are salts that work together to maintain pH stability.  Most things in biology, including the active ingredients in a vaccine, will fall apart if the pH is not somewhat neutral.  A certain pH can be set and maintained in a liquid by adding these compounds together in a certain ratio that can be calculated.  These compounds are charged, which means they are ions.  Sodium, potassium, and phosphate are also referred to as electrolytes in the context of physiology.  They are common and important parts of every biological system, and are present in much of what you consume and excrete.  Sodium phosphate can be prescribed in large doses where it acts as a laxative for the purpose of bowel cleansing prior to a colonoscopy.  Different kinds of phosphates are also commonly used in fertilizers, because plants need them too.   

4.       Sucrose (C12H22O11), 0.0019 grams
You already know all about this one – it is table sugar.  It is used most often in foods and beverages to make them taste sweet, as we all know.  But its function in a vaccine is the same as sorbitol (see above).  It stabilizes the active ingredients of the vaccine in their dehydrated state at different temperatures.

5.       Sodium chloride (NaCl)
You are also very familiar with this one – table salt.  As with sucrose, its place in a vaccine has nothing to do with its more familiar culinary use.  The correct balance of sodium (Na+) and chloride (Cl-) ions is important for the stability of any biological compound in a similar way that pH balance is important.  The active ingredients (i.e. harmless viruses) would likely fall apart without the proper concentration of sodium chloride.

6.       Hydrolyzed gelatin (protein), 0.0145 grams
If the first thing that comes to mind here is Jell-O®, then you are on the right track.  Yes, gelatin is the main ingredient in Jell-O®.  But what exactly IS gelatin?  Well, it is a protein called collagen that twists around itself like strings within a rope.  Collagen is what your connective tissue is mostly made out of, and you have more collagen in your body than any other protein.  ‘Hydrolyzed’ means that the long strings of protein are broken down into smaller fragments by enzymes and heat.  In a vaccine, these protein fragments function in stabilizing the active ingredients.  And all proteins are just a chain of the same various amino acids that exist in all living things.

7.       Recombinant Human Albumin (protein), ≤0.0003 grams
Albumin is a common and very abundant protein found in the blood plasma of animals.  Its job is to maintain the proper balance of water and ions in the bloodstream.  When growing the viruses that are used in the vaccine, this would be an important ingredient to have in the liquid cell culture growth medium.  Because one dose of the M-M-R II® vaccine has ‘less than or equal to’ 0.3 milligrams of albumin, this may be an indication that its presence is residual, leftover from the production process after purification.  Regardless, it may function as a stabilizer in the vaccine in a similar way as it does in the bloodstream.  This is a human protein, but it does not come from a human source.  The adjective ‘recombinant’ here means that it was produced in another organism (probably yeast cells) by inserting the corresponding human gene into that organism, growing it, and extracting and purifying the albumin protein.  Because it is so abundant in the blood, it would certainly be easier to obtain from human blood donors.  But apparently Merck went out of their way here to eliminate that sort of thing from their production process.

8.       Fetal Bovine Serum, < 1 part per million
This is an extract of a mixture of various compounds present in the liquid fraction of blood.  And yes, ‘fetal bovine’ indicates that its origin is from cow fetuses, which may sound alarming.  Like albumin, serum is an important ingredient in the liquid growth medium that cells are grown in where the vaccine viruses are being cultivated.  For many years, scientists tried in vain to grow cells from tissues and organs in a test tube.  It wasn't until someone tried adding serum that it finally worked, and it has changed medical research related to every disease imaginable ever since.  Like the albumin, it is probably only listed as an ingredient in the vaccine because it may be present in residual amounts after the vaccine viruses are extracted and purified from where they were grown (1 part per million =  0.0001%).  Work is ongoing to determine which components of serum are important for cell growth so that they can be produced without needing to source them from animals like cows.

9.       Other Buffer and Media Ingredients
This is listed here as an ingredient just in case trace amounts of the compounds from the liquid growth medium that viruses were cultivated in are still present after purification.  Because as Billy Idol once observed, “there is nothing pure in this world”.  This is especially true on a molecular level, where 99.999% is about as pure as anything gets.  The culture media used in the production of the viruses for this vaccine is called Medium 199 and MEM.  Included in these media are nutrients that cells need such as vitamins, amino acids, salts, and glucose.

10.   Neomycin, 0.000025 grams
Neomycin is an antibiotic.  It is added to the liquid that the viruses are cultivated in to prevent bacteria from growing and fouling the sample.  Similarly, it is left in or added to the vaccine to act as a preservative by keeping the vaccine sterile.  Neosporin® is named after neomycin because it is a main active ingredient.  It is also in other creams, ointments, eyedrops, eardrops, and the like.  When I was a child, I learned that I was allergic to the antibiotic penicillin following treatment of an infection.  As with penicillin and other antibiotics, some people can be allergic to neomycin – so it is important that it is listed as an ingredient here.  A doctor administering a vaccine would be expected to be aware of this.

There you have it: those are the ten inactive ingredients in the vaccine for measles, mumps, and rubella that is commonly administered in the U.S.

The toxicity of these (or any food/drug ingredient) has more to do with dosage of a substance rather than the substance itself.  It is the job of the FDA to regulate safe amounts of any of these compounds in this vaccine, just as it is their job to do so with everything else that we consume or use for medicine in the U.S. (with the exception of dietary supplements).  A thorough evaluation of past scientific studies on adverse reactions correlated with (but not necessarily caused by) the use of the M-M-R II® vaccine has been published in peer-reviewed literature here, though it should be noted that this literature review was commissioned by Merck.

To me, it seems that the M-M-R II® vaccine contains a minimal amount of inactive ingredients in minimal quantities, and it appears that Merck went out of their way to use ingredients that are already present in the human body wherever possible – even when cheaper alternatives could be used without compromising quality. 

The ingredients in other vaccines vary, and more information can be found about them on this useful website put together by the University of Oxford.  The safety of many other common vaccines has been objectively reviewed in a very nice recent academic publication that can be found here.  And this report has no attachment to a pharmaceutical company, advocacy group, or any other potential conflict of interest.