Tuesday, July 12, 2016

The History & Science of Vaccination

Previously, I talked about the vaccination debate in the context of two opposite views: the good of the public and the good for individuals. Immunization advocates typically argue that the science supports the safety and effectiveness of immunization as an absolute good. Immunization opponents argue that the science is incomplete, and that this incompleteness is actually a deliberate act; they argue that drug companies and doctors actually overlook science that doesn't support their view that immunization should be universal and complete.

Vaccination is actually a very old practice. There's evidence that in the 1100s, the Chinese, Turks, and Africans used materials contaminated with smallpox to immunize against that disease. We often think of smallpox as being very lethal. It's true that one series found a case-fatality rate of 62%. On the other hand, smallpox epidemics existed during times that were less technologically advanced. Moreover, some subtypes of smallpox are more lethal than others, so overall the fatality rate is about 30%--still pretty scary! Mild cases exhibit a fatality rate of less than 1% (CDC, 2007), and inducing "mild" cases was the basis of the crude immunization techniques in the ancient world.

The story we are most familiar with is the work of Edward Jenner, who in 1796 used material from the lesions of cowpox, found on the hands of milk maids, to immunize against the similar virus, smallpox. Later, Louis Pasteur and Emile Roux used the blood of a rabies-infected mouse to immunize a boy who had been bitten by a rabid dog. Allowing the blood to dry out for nearly 2 weeks "devitalized" the virus, which must live in blood. This process preserved the viral proteins, however, and the boy's immune system could recognize these proteins, and act on them, reprogramming itself to fight the virus.

Rabies has a case-fatality rate of about 99%. Most victims die because their immune systems can't act fast enough to fight the virus before it kills them. The cause of death is general neural failure. Basically, nerve functions, including the drive to breathe, fail. Introducing a germ--or parts (proteins) of a germ--allows the body to see and begin to recognize it. There are two main branches of immunity, innate and acquired. Innate immunity is prompt and readily attacks germs, but it does a sloppy job and often misses a lot of them. Those germs that get past the innate immune cells go on to cause disease.

Acquired immunity engages a series of very specialized cells that go through a complex dance which results in the generation of very specific, highly targeted antibodies and cells that are highly lethal to those germs. Let's say you get a cut on your finger. Immediately, special cells in the skin and blood go after whatever germs got into that cut. But at the same time, a few cells "read" the proteins on those germs and send signals to other cells that start to rearrange their own DNA in order to develop a profile of those germs. They then grow and divide, these new-reprogrammed cells, to create highly specific cells ("killer cells") and chemicals ("antibodies") to eliminate those germs.

If there are any immunologists out there reading this, I know I'm simplifying this quite a bit. The thing is this is a well-understood mechanism for how we fight off disease, which we are exposed to every day.

It's possible to take advantage of this feature of our biology to prevent disease. Exposing people to germs or parts of germs, whether viruses or bacteria, can engage this system of acquired immunity. Once the acquired system has been activated, a lineage of these specialized cells will persist in the body, one line for each unique germ. These are called memory cells. Because of these memory cells, whenever the body is re-exposed to a given germ, instead of it taking 7-14 days to develop a targeted response, it takes only hours to days.

One of the important features that we have to know about is the stability of whatever germs we're trying to protect ourselves against. Smallpox is very genetically stable. Cowpox is also very stable, and presents a very similar protein "picture" to smallpox. Again, I'm simplifying here to make a point, and that is that genetically unstable germs are more difficult to vaccinate against. For example, the common cold still defies attempts to develop a vaccine. That's because the viruses that cause the common cold (mainly rhinoviruses or "nose viruses" literally! There are few less common viruses that cause colds) are prone to mutate. 

This is also why we get multiple colds. Cold viruses mutate.

But if the infecting agent is genetically stable in the wild, and you either had the infection before, or you got a vaccine against it, your memory cells ramp right up to fight the infection if you run into it again. 

This is also the case with HIV, for example. HIV mutates a lot! Those mutations often cause viruses to become inactive, but it also often gives them a "stealth" characteristic that makes it hard to the acquired immune lineage to recognize that this was seen before, say in a vaccine shot. It's also why some people can have multiple strains of HIV at one time.

Unfortunately, this system isn't perfect, and we don't fully know why. Hepatitis B vaccine typically provides protection to 96% of healthy adults (Merck & Co., 2014). Looked at another way, about 1 in 24 vaccinated adults will not develop immunity to hepatitis B when vaccinated properly. I am one of those people. I was vaccinated four times when I was ER nurse, and I never developed antibodies to give me immunity to an infection that at the time had an incidence rate among ER personnel of 35%!

Infanrix, a product that immunizes against diphtheria, tetanus provides, and whooping cough reportedly provides 100% immunity for the first two conditions, and 84% of children achieve immunity for whooping cough (GlaxoSmithKline, 2016). 

Last year, the flu vaccine--which mutates a lot--had a protection rate of 47% (CDC, 2016). Not all that great.

One study that looked at duration of immunity over time found that this was disease-dependent, and that actually having the disease tended to confer more durable immunity than having been vaccinated for it (Amanna, Carlson, & Slifka, 2007).

In short, vaccination works most of the time for its stated purpose. In cases like the flu, most years you could flip a coin to predict who it will work in (until we figure out why, at least). And while a lot of people get protected, that protection can wane over time, necessitating booster shots.

The U.S. now immunizes for 18 diseases in 35 doses plus approximately another 15 doses if one includes annual flu vaccines. Many of these are given in combinations (e.g., measles, mumps, rubella), or several in one child health visit, and on several occasions, since in many cases a single shot isn't enough. 

Amanna, I.J. Carlson, E. & Slifka, M.K. (2007). Duration of humoral immunity to common viral and vaccine antigens. New England Journal of Medicine, 357: 1903-1915.

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