The Antigen Gambit Part 1 – Or – Can We Understand Immunology Through Addition?

Posted by: passionlessdrone on: April 14, 2010

• In: Antigens | Autism | Biological Plausibility | Early Life Immune Activation | Fever | Genetics | Gross Over Simplification | Immunology | Paul Offit | Some Jerk On The Internet | Toll Like Receptors | Uncategorized | Vaccines! | Willing Disbelief
• 8 Comments

Hello friends –

I hate to write another vaccination related post, but I keep on running into the same, tired argument, and thought it might be nice to have a single place to list and link the reasons that one of the most commonly used defenses of why we don’t need to study the vaccination schedule can be dismantled. The scary part, the really fucking scary part, is how easy it is to deconstruct the metrics being provided by experts as to why questioning the process of vaccination need not be thoroughly evaluated, and how people that ought to know better keep regurgitating the antigen gambit despite its obvious shortcomings when held to the most primitive logical tests.

For some background, lets start with basic immunology and the hows and whys of how vaccines actually work. But even before that, lets be clear: Vaccines work. I have absolutely no doubt that the purpose of vaccines, providing protection against microbial invaders is successful, and saves millions of lives every year. What I’m not so sure of,  is whether or not this is the only thing our increasingly aggressive vaccination schedule has been accomplishing.

The functional success of vaccination is that we have crafted a technique that allows us to train our immune system to recognize some very nasty, dangerous, and deadly bacterial and viral pathogens. How is this done? Well, it turns out that at a very detailed molecular level, many bacteria and viruses have very specific patterns on their exterior, for our purposes, an immunological fingerprint that identifies, for example, the tetanus bacteria from the diphtheria bacteria. These fingerprints are known as antigens, and our immune systems use them to store a memory of particular pathogens we have been exposed to, so the next time such a pattern is encountered, a robust immune response can be mounted rapidly, before the pathogen gets a chance to reproduce and get us sick.   The memorization of these molecular patterns, the fingerprints of specific bacteria and viruses, is the foundational premise of vaccination; by presenting these antigens to our immune system in a hopefully(?) harmless way, we train our immune system to respond to these invaders without actually having to endure the virulence of the actual bacteria or virus. Making things a bit more complicated, some pathogens have more than one molecular face to present, and as such, more than one fingerprint is necessary for our immune system to recognize. Some others, such as flu, regularly shift their molecular fingerprint; this is why there are seasonal flu shots, each year scientists must make educated guesses as to which particular influenza fingerprints will be most prevalent; when they guess correctly, the vaccine mostly works, because we have trained our immune system to see that particular antigen pattern. Other pathogens, like HIV, undergo such rapid transformation of their outward facing molecular structure that tailoring a molecular portrait of them has proven exceedingly difficult.

So, again at a very high level, vaccines work because they present antigens, immune fingerprints, from viruses or bacteria to our bodies, without the associated virulence of the organisms. The hows of creating the antigens without the problems of actual infection aren’t necessary for this discussion; lets just assume that for our purposes, you can have bacterial or viral fingerprints introduced in a vaccine without having to worry about the traditional ramifications of the actual bacteria or virus they came from. Great!

Given that, lets imagine you are a skeptic and are a bit bothered by the fact that our existing vaccine and autism research seems to be wholly comprised of studies involving either thimerosal, or the MMR. It seems a bit confusing that these two types of studies are sufficient for us to have certainty that the act of vaccination itself, or other vaccines administered at very different ages might be contributing to our apparent observations of increases in autism (or other behavioral or autoimmune disorders). If you raise a question involving this glaring blind spot in our research, a lot of the time you’ll see a response like some of these:

The only thing that makes biological sense in the discussion really is antigens and excipients and if you look at that, today’s kids get FAR fewer than say, my generation.

What is relevant is the number of antigens, and not the number of vaccines, that matters. Antigens are the active part of the vaccine which stimulates the immune response.

Another point directed to those who think that multiple vaccines overload the immune system. In actual fact, even though we are vaccinating against more diseases than in the past, we are actually using fewer antigens (the part of the vaccine which stimulates the immune response) in these vaccines than was previously the case.

You get the picture;  the only measurement of interest is the number of antigens in vaccines.  To be completely fair to some people that use the antigen gambit, it is in response to its equally simplistic counterpart, the ‘Vaccines Overload The Immune System’ gambit. That’s no excuse, at the end of the day, the people using crank arguments are supposed to be the cranks. What worries me is the people using the antigen gambit, are in many cases, the experts, and in the rest of the cases, folks that have listened to the experts, and parrot something that sounds sciency. It is a frightening day when you realize that if infectious disease experts had a reason, a real reason, we shouldn’t study the entire vaccination schedule, they’d provide one better than the antigen gambit.

The tour de force take down of the Vaccines Overload the Immune System gambit is “Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?“, by Paul Offit and others. It’s my guess that this document, published in the highly read Pediatrics journal, plays a big part in people believing that the only important thing about the vaccine schedule is the number of antigens involved. Here is the abstract:

Recent surveys found that an increasing number of parents are concerned that infants receive too many vaccines. Implicit in this concern is that the infant’s immune system is inadequately developed to handle vaccines safely or that multiple vaccines may overwhelm the immune system. In this review, we will examine the following: 1) the ontogeny of the active immune response and the ability of neonates and young infants to respond to vaccines; 2) the theoretic capacity of an infant’s immune system; 3) data that demonstrate that mild or moderate illness does not interfere with an infant’s ability to generate protective immune responses to vaccines; 4) how infants respond to vaccines given in combination compared with the same vaccines given separately; 5) data showing that vaccinated children are not more likely to develop infections with other pathogens than unvaccinated children; and 6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago.

The biggest problem here is that the acknowledged, ‘implicit’ concern is that multiple vaccines may overwhelm the immune system.  The concern we should be more concerned with is, can vaccines modify the immune system  in ways that we cannot predict?  This is a question that is not addressed here, but if your premise starts with the wrong question, or in this case, a bad question your conclusions shouldn’t be worth much.

All of the bullet points provided suffer from one or more maladies, including a foundational structure of gross over simplifications, insulting the intelligence of the reader, or in one case, wildly optimistic claims of a study conclusions; the same kind of thing what would get you a special article by the Chicago Tribune if you  recommended children with autism try not to eat wheat for a few weeks and see what happens. 

For this post, we’ll just focus on the last bullet point, and the text that supports it:

6) the fact that infants actually encounter fewer antigens in vaccines today than they did 40 or 100 years ago

This is the lead in for this question:

Parents who are worried about the increasing number of recommended vaccines may take comfort in knowing that children are exposed to fewer antigens (proteins and polysaccharides) in vaccines today than in the past.

To prove this comforting point, the authors provide this fancy table:

 

(Bigger view on the link to full paper – they don’t have this table exploded as its own supplement link).  The good news is in green here, as noted in the text, the only reduction count in the vaccine schedule after 1960 was the change from DTP to DTAP. 

The bad news is that, if counting antigens were a meaningful metric, of well, anything, the chicken pox vaccine, Varicella, now contains more antigens than the rest of the shot schedule combined. 

This puts us in somewhat of a conundrum.  If the ‘number of antigens’ in vaccines is what is relevant, does this mean that the Varicella vaccine puts nine times more stress on the immune system than the Pneumococcus vaccine?  Does the Varicella vaccine initiate an immune response sixty nine times more strenuous  than the diphtheria component of the DTAP vaccine?  [Good luck finding a study to measure the innate immune response to any of those vaccines in a pediatric population.]

The DTAP was licensed in the 1980s, but Varicella didn’t get licensed until 1990; so this means that children who got DTAP, but didn’t get Varicella, got far fewer antigens, half as many, than children born just a few years later.   Is this meaningful?

Here is an interesting way to view the question.  Imagine the CDC was addressing a set of parents whose children was born in 1985 who were concerned about those vaccinations overloading the immune system of their children, and this was the response:

Parents who are worried about the increasing number of recommended vaccines may take comfort in knowing that your children were exposed to fewer antigens (proteins and polysaccharides) than in vaccines today.

Does this sound like a good argument?

We might also take a look at how frequently children experience mild side effects from vaccination, according to the CDC web site.   Fever is an indicator of innate immune activation, though you will occasionally see arguments made that it is insufficiently characterized to draw conclusions from, but if  we are trying to understand if addition of antigens is a useful measurement or not, it would seem the rates of side effects are valid goalposts.  Here are some quotes;  there isn’t a fancy table of this information yet.  

• Varicella: Fever (1 person out of 10, or less) [69 antigens]
• Pneumococcal: Up to about 1 out of 3 had a fever of over 100.4 degrees Fahrenheit, and up to about 1 in 50 had a higher fever (over 102.2 degrees Fahrenheit).  [8 antigens]
• MMR Fever (up to 1 person out of 6) [24 antigens]
• DTAP: Fever (up to about 1 child in 4) [4 – 7 antigens]

Now that is curious.   According to the CDC, the vaccine with the most antigens causes fever far less frequently than vaccines with many times fewer antigens in them.  If we can use addition to gain comfort from the fact that the current vaccine schedule includes fewer antigens than it used to, how do we incorporate in this information? 

But if we can’t use addition for our purposes?  What if, in fact, the system we are interacting with is much, much too complicated to be usefully outlined with simple addition?  What if antigens aren’t the only relevant measuring point in evaluating vaccine impact on the immune system?   In this case, why use the reduction in antigens in vaccines as an argument to ‘address parents concerns’?  Why has such a gross over simplification achieved ubiquity in the blogosphere and indeed, why was it promulgated by the most frequently interviewed physician when the subject is autism and vaccination? 

Ponder the above at your own risk.

–          pD

Tags: Addition, Antigen, Autism, Fever, Gross Over Simplification, Offit, Vaccines!