An Overview of Vaccines

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A few days ago, a friend kindly broke my long writer’s block (so many subjects, so little time), with a question about vaccines. She had heard a radio ad for a study in which a new AIDS vaccine candidate would be tested. The ad stated that the vaccine was perfectly safe. Is that possible, she inquired? While I can’t speak to that particular vaccine in question, I thought I’d provide a dose of my knowledge on the kinds of vaccines and how they might (or might not) be safe, effective, useful, and so on.

Vaccines are a rapidly expanding field of the medical world, and there are many family practice jobs like the ones from Leap Doctor and research jobs available specifically in vaccine study. Most of us have a working definition of vaccine: that shot they give you so you don’t get sick. This is a good generalization for the everyday person. Of course, vaccines can be given orally (polio), nasally (mostly experimental), by gene gun (also experimental), as well as via injection. And there’s different types of injection from the “stab-and-jab” of the subcutaneous (aka: anywhere under the skin) injection, to the more carefully poked intravenous (aka: into the blood) injection. Beyond that, vaccines are indeed supposed to prevent illness, in essence, by giving you a little bit of what could ail you in an attempt to get your body on the permanent alert.

Without going into pages and pages of detail (and trust me, there’s books and books of detail, and even larger books of what we don’t know), let me explain how your body goes on permanent alert at the sight of a vaccine.Your immune system has scads of different components that I’m just not going to touch on here. The important parts for this discussion are the big two, your T-cells and your B-cells (and why are they called thusly: A different essay for a different time). These cells are coated in claw-like proteins that respond very specifically to different proteins that enter your blood. Each T-cell/B-cell has its own set of specific claws and thus responds to a different protein. How does this happen? Well, through the miracle of genetic recombination, which is a nice way of saying “useful slip-ups,” your body never produces the same set of “claws” twice, no matter how many times it runs through the same T or B-cell assembly line. Your body compensates for this by having a very rigorous T and B-cell selection process (think Marine Corp boot camp, only more deadly) so that you don’t produce cells that think your own proteins are suspect (this does, however, occasionally happen anyway, causing all sorts of terrible autoimmune disorders). So a system of studied inefficiency leads to a very elegant and wide panel of possible immune cells.

Why is this important? Because viruses, bacteria, and parasites, the Big Three in the germ world, contain more individual differences than you or I or even Stephen Hawking for all his universal wisdom can imagine safely without our heads exploding. So your body has to be equipped to recognize tens of thousands of proteins without ever having seen them before. And that’s what’s so amazing about the immune system – somewhere in your body is a T-cell or a B-cell that can bond and respond to a protein that you’ve never encountered, that perhaps has not yet been created. No kidding.

But one cell in a body of trillions is not a particularly good guard against, say, an invasion of measles. If measles invades, your guardian cell has to find it, bind to it, send out alert signals, cause your immune system to swing into action, and try and save you. As history proves, disease is often faster than your immune system. This is where vaccines come in.

Not only does your immune system have an incredibly complex recognition system, it also has a memory system. If you get measles as a kid, chances are you’ll never get measles ever again – your immune system makes sure of it.

T-cells are killers. When a T-cell finds its target, it proliferates, creating an army of T-cells to fight off the invader using a complex series of deadly weapons, especially poisons. Like a Cold War spy stereotype, your immune system is very good at poisoning its enemies. Once you recover, some of those T-cells are given desk jobs for valor in battle, and become T-memory cells, keeping a watchful eye on the borders of your body in case the invader ever returns. When a B-cell finds its target, it not only proliferates, it turns into a little war machine and begins pumping out antibodies. Antibodies are like little disembodied claws with flags on their wrists. They float around, bind to invading germs and act like signal beacons for other immune cells who come and kill the virus (either through the T-cell poison method or by simply ingestion. We’re also very good at eating our enemies). These antibodies don’t disappear when you recover. Instead, they float around like a satellite monitoring system (think of Reagan’s “Star Wars” plans), ready to act in case of another attack.

Vaccines, then, are intended to be a safe induction of that memory response. Your given an injection of a harmless form (or something very similar – more on this later) of the germ in question, you mount a successful immune response to it, and then your body remembers the enemy, so that if it invades, you kill it before it has the chance to make you sick. Memory not being perfect, you sometimes have to get a booster shot a few years after the initial vaccine, and sometimes you have to get a series of shots (hepatitis, for example), in order to build up the level of memory you need to protect you from particularly nasty diseases. Antibodies are of chief importance here, as they are the floating alert system that can save you – you want to create as many antibodies as you can to ensure permanent immunity.

Vaccination isn’t a modern, post-industrial invention. In fact, 11th century physicians in China and India were known for injecting the pus from smallpox lesions into their patients. The hope was to cause a mild form of the disease and grant permanent immunity thereafter (Smallpox being a “once in a lifetime” virus). This process, now called variolation, is not the most efficient, nor, as you might imagine, the safest way to immunize a populace – despite the best efforts of these doctors, smallpox persisted on a wide scale until the last century.

Edward Jenner is the name commonly associated with vaccines, although if you had asked people in the 1780s who he was, the educated would point to him as a great birdwatcher, and author of a seminal paper on Cuckoo behavior (the same people would later accuse him of perhaps emulating his beloved birds). In 1796, in a completely unethical experiment, Jenner injected a young boy with pus from a woman’s cowpox wound, (cowpox is a benign bovine relative of smallpox and was often caught by milkmaids), and then two weeks later deliberately infected the boy with smallpox (that would be the unethical part). Fortunately, the boy survived, and Jenner’s name went down in history (although it was another man, William Woodville, who conducted the first large-scale study to prove Jenner’s one-time experiment).

The way science works is not always fast or forward. Often, scientists are no more progressive in their labs than they are in their lives, and reflect the culture around them. This is probably why it took another 100 years before vaccines were given a second chance, when Louis Pasteur invented his rabies vaccine (and coined the word “vaccination”). Other vaccines, however, were a long time coming.
Why did it take humanity so long to embrace what has become a modern mainstay of public health policy? The single biggest reason is probably a lack of technology. “Germs,” as we know them remained a somewhat murky theory until the early 1900s, first with Koch’s postulates involving disease elements (which established how to prove something actually caused disease), and second, with the development of microscopy. Bacteria-observing microscopes had been around throughout the 1800s, but microscopes that could observe viruses (which make teensy-weensy seem large) weren’t developed until the 1930s. Prior to this, the cause of any given disease was mysterious – for example the term “malaria” comes from the Italian words for bad air (mal aria), because the Romans believed swamp gas caused what we now know is a parasitic illness. We couldn’t see what killed us, so we tried to explain it the best we could – bile imbalances, bad air, evil spirits, etc…

Now that you have some history, I’ll skip ahead to the point in time that is the present. We know what ails us most of the time, we can sometimes look at it, and if we’re even luckier, we can make a vaccine to prevent people from getting it. To that end, there are currently four types of vaccines, though only three are in widespread commercial use. Some of these are safer than others, which gets back to the original question.

The first kind is the “Live Attenuated” Vaccine. This type is probably the most common of the vaccines you’ve had, as it includes measles, mumps, rubella, and chicken pox vaccines in America. Military recruits sometimes also get the live attenuated vaccine for adenovirus and yellow fever, and some of us and/or people from other countries may have gotten the live attenuated polio vaccine as children. So what is it? A live attenuated vaccine is at heart the same virus that can make you sick. It has, however, been effectively brainwashed into submission. This is usually done by growing the virus in the cells of another animal until it no longer thinks of itself as a “human virus.” This could, for example entail injecting it into a rabbit, removing it from the rabbit, injecting it into another rabbit, and so on and so forth for several generations. Usually, the progression is a little more complex. For example, the measles vaccine currently in use was isolated from humans in 1954. It was then grown in human kidney cells (in a dish), human amnion cells (the fluid that surrounds babies in the womb), sheep kidney cells, and chicken embryo cells. After this, the “brainwashed” virus doesn’t make us sick anymore, but it’s also not quite as good at inducing memory as the original virus, so it takes a few shots to create a protective level of antibodies (for measles you usually get two shots, one as a baby then another between the ages of 6 and 12). Live attenuated vaccines are generally very effective and very safe, and some, like the polio or adenovirus vaccine, can be given orally as opposed to injected. So what’s the problem? Well, occasionally, the virus will revert to its original nasty self. You’ve already mounted an immune response, so you’re safe, but unvaccinated or immune-compromised people around you may not be. So you may not get sick, but you can make others sick (which does wonders for your social calendar). This tendency to revert is one of the biggest obstacles to making effective live attenuated vaccines for most viruses.

There is an off-shoot of the live attenuated vaccine that has returned to use in the past four years – the viral vector vaccine. This sounds big, but what it really means is “using a harmless virus that looks a lot like the bad virus to induce immunity.” You know it as the smallpox vaccine. The vaccinia virus, aka cowpox, is still used to provide immunity to smallpox. However, as I’m also sure you know, side effects do occur, and occasionally, the harmless vaccine can, in fact, cause disease. Experiments are currently underway to take even more harmless viruses and give them some of the genes of the harmful viruses, again providing immunity without disease. At least one ebola vaccine trial in animals has so far been very successful with this model, and some experimental HIV vaccines have shown promise using this method.

The second kind of vaccine is the Inactivated or “Killed” virus vaccine, and includes the vaccines for influenza (the yearly flu shot), hepatitis A (only given to travelers), Japanese encephalitis, some polio vaccines, and rabies. This vaccine is exactly what it sounds like: virus that has been “killed” (disregarding the debate over whether viruses are actually “alive” in the first place). Dead virus can’t make you sick, but you still mount an immune response to it. Often, viruses are inactivated with harsh chemicals like formalin or something called beta-propriolactone (not on the quiz). On the surface, these vaccines sound ideal. The big problem is this: viruses are super-duper-small, so what if you don’t kill every single one? What if another virus sneaks into the batch? In 1950, a batch of polio vaccine wasn’t “quite dead yet,” and led to over a hundred children getting polio from their vaccinations. Last year’s flu shot was in jeopardy because of contaminated culture materials. The third problem is that some viruses, like influenza, change so frequently that last year’s vaccine is no longer effective. This is why you have to get a new flu shot every year – you’re facing a new and very different flu every winter. Last but not least, while our bodies do respond to killed viruses, they don’t mount quite as large an immune response as to live viruses, especially if you’re an adult. So the flu shot is not 100% effective in the elderly population, who sadly, is in the greatest need of protection.

The third type of vaccine is the Subunit vaccine, which in humans is currently a family of one: the Hepatitis B vaccine (that series of three shots, each one more painful than the last). Experimentally, many subunit vaccines are in the works, but only the HepB series has been commercially and medically successful so far. The theory is straightforward: take the virus apart, purify out the bits that your body can respond to, leave behind parts that make the virus complete (and therefore dangerous) and use the reactive subunits for a vaccine. Viruses are often little bits of genetic material inside a series of coats. So if you take just the jacket and inject it into the patient, you should theoretically get a great immune response with no chance of disease. Hepatitis B outer proteins are grown in yeast cells (yeast, our usually harmless beer-making friend! How we love yeast), then purified and injected into your arm. This works well for hepatitis, but so far nothing else. Why? Well, first you have to know which bits of the virus will cause a good immune response. Then you have to find a way to produce/extract/purify just those bits. Then you have to test them, and oddly enough, even if you’ve got the first two things down pat, you often don’t get a very good immune response. We don’t really know why, but subunit vaccines are just not as effective as whole virus vaccines. So while in theory these vaccines are perfect, in practice, they are mostly confined to lab experiments. The HepB series, however, works very well, so don’t worry about that one.

The last type of vaccine is purely experimental still. The DNA vaccine is a variation of the subunit vaccine, and basically consists of a piece of viral genetic information injected directly into your cells. The gene or genes would be produced in your cells, and the viral proteins displayed on the outside of your cells like giant red flags to your immune system. Your body would then produce a fairly good immune response. As farfetched as the idea of injecting DNA straight into your cells to cause immunity sounds, lab results in animals have been very successful. At least one lab is working on a DNA vaccine for tuberculosis (a bacteria, but the idea is the same) and producing decent results in mice. There’s too much we don’t know about this approach to make it useful in humans yet, but it looks promising.

To get back to the original question: are vaccines safe? The answer is yes. Perfectly safe? Well, that depends on the type of vaccine. At the moment, the only “perfectly safe” vaccine is the subunit vaccine (with the caveat as long as your not allergic to what its grown in, like yeast or eggs – the vaccine itself, however, is perfectly safe). The new viral vector vaccines (not smallpox), that offshoot of live attenuated vaccines are incredibly safe, and live attenuated and killed virus vaccines are almost completely safe. There have been accusations that the thimerosal, a preservative in some vaccines is linked to autism, but the evidence is shaky still (and is, again, another essay for another time), and due to public pressure, thimerosal was eliminated from U.S. vaccines in 1999. Is the particular experimental AIDS vaccine that my friend heard advertised on the radio safe? It’s probably mostly safe, but not perfectly so. I doubt very much that there’s any chance it could give you HIV, but there might be a chance of many side effects. Any vaccine, especially for such a deadly disease, that’s made it to human trials must be a very safe vaccine indeed, but in some ways, perfect safety is still a trade-off for immune response, so it may be perfectly safe, but not perfectly effective. The perfectly safe, perfectly effective, perfectly priced vaccine is still the Holy Grail of vaccine technology, and the great quest of many budding graduate students.