Better Living Through Chemistry? Vaccine Resistance and Illness

Vaccines effectively prevent many infectious diseases, but they also exert powerful selection pressure on microbes, and evolving vaccine resistance suggests that it may be time to alter our strategy from biological whack-a-mole to chess.


| November 2014



Vaccine vial

Vaccines help our adaptive immune system recognize viral invaders before they can make us feel ill, but they also represent significant selection pressure, forcing the virus to evolve or die.

Photo by Fotolia/singburi

In Unnatural Selection, Emily Monosson shows how our drugs, pesticides, and pollution are exerting intense selection pressure on all manner of species. She examines the species that we are actively trying to beat back, from agricultural pests to life-threatening bacteria, and those that are collateral damage—creatures struggling to adapt to a polluted world. Eye-opening and more than a little bit disturbing, Unnatural Selection considers the effect humans have had on the evolution of other organisms and suggests ways we might decrease our evolutionary footprint. The following excerpt is from chapter 2, “Prevention: Searching for a Universal Vaccine.”

How Does the Immune System Exert Selection Pressure?

Our immune system is extraordinary. Like a 3-D printer on steroids, we create antibodies in response to trillions of novel antigens (which, by definition, are substances that elicit an immune response). We are constantly challenged with antigens. I might be shopping at the local Food City in the midst of flu season (and haven’t yet gone for vaccination). As I stand in the checkout line with my milk and orange juice, a shopper coughs. I inhale, and flu virus forced from her lungs enters into mine. My innate immune system kicks into gear. Like Homeland Security this is the system that patrols my body—ready to act against threatening foreign objects no matter flu, pathogenic bacteria, or some other unfamiliar entity. Cells belonging to this system will engulf the offender and release an arsenal of chemical defenses. If it’s a viral infection, “natural killer cells” will arrive, creating a sort of firebreak by causing cell death. I may run a fever and drop into bed with muscle pain. This collateral damage is the cost of nonspecific defense, but it buys my body time to initiate a more specialized response by way of the adaptive immune system.

Most of us are familiar with antibodies produced by the adaptive immune system, but it also produces “killer cells.” Both are exquisitely specific for antigen. Each cell of this adaptive system is recruited from a huge storehouse of immune cells just waiting to be selected—much as I imagine Amazon or Netflix warehouses carry an unimaginable array of books or movies. When we come into the world we are equipped with a universe of immune cells bearing receptors formed through a process of genetic recombination. Some of these are called B cells. These are the cells that make antibodies. When B cells interact with antigen they become activated and undergo a process of mutation and selection. Those producing antibodies that best fit the pathogen (in this case the flu) survive—a sort of Hunger Games for immune cells. Most will produce ineffective antibodies. Some produce antibodies against our own antigens—not a good thing—and those die early in the process. The cells that produce the most-effective antibodies are cloned. The process continues, ratcheting up the specificity and refining the antibody. It can be a week or two before the adaptive immune system is fully effective—which means that sometimes viruses evolve the means to escape immunity; or that we may be feeling the effects of infection for a while before the system kicks in. It’s a lot of work but well worth the effort. Once exposed, the adaptive system provides us with immune memory. Long after the offending pathogen is gone, whether bacterial or viral, a set of immune cells will circulate, acting as sentries and responding far more rapidly, days rather than weeks, should the same, or similar, invader come knocking again.

The flexibility of the adaptive response in part explains how relatively slowly evolving creatures like us keep pace with viruses—by surviving the first round we are better prepared, if not fully prepared, for the next. The influence of viruses on our genome in general and our immune response in particular is significant. Evolutionary biologist Michael Worobey and colleagues note that the viruses that have shaped our “battle-worn genotypes and phenotypes” may well influence characteristics that have little to do with pathogens. So tightly intertwined is our evolutionary history that understanding the human–virus relationship might someday help us rein in the emergence and spread of new viruses. If we ever doubt our defenses, Worobey’s group suggests we consider all the pathogens and all the flu subtypes that didn’t make it. While we may feel we are surrounded by pathogens, it could be far worse. But there is a flip side. Our immune system imposes a powerful selection pressure. If we didn’t mount a response, there would be little if any naturally occurring selection pressure on viruses. The result is an evolutionary triumvirate: high rates of reproduction, genetic variability, and strong selection pressure. Rapid evolution is inevitable. All of which raises some potentially troubling questions about vaccination: if immunity drives virus evolution naturally, could vaccination also drive evolution? And, since pathogens and immunity evolved in tandem, could vaccination somehow alter the development of immunity?

Vaccine Resistance and the Evolution of Virulence

Inevitably, as flu season arrives, the local newspaper runs a story by an herbalist or naturopath touting the power of our immune response. Nature, they write, has provided us with a formidable defense—why interfere with it by resorting to vaccines? It is true that many of us, most times, are capable of fending off influenza. But history is also littered with bodies whose natural immune response was overwhelmed. In 1918, it was the younger and fitter populace that succumbed. If the survival and fitness of the human population is our only concern, then the argument that humans and viruses have coevolved works. After all, humanity has survived countless plagues, and evolution applies not to individuals but to populations. An individual may or may not possess a beneficial mutation, but it is the population that evolves—should that beneficial mutation or gene become widespread. And so the argument that we are all well enough endowed by nature falls short when we begin to value each and every member of society, because some of us are certainly more susceptible than others. Until we devise a better alternative, vaccines are our best defense. But still, the questions remain. Is there an unanticipated downside to vaccination?

Most flu-vaccine production, despite all of our technological know-how, begins much as it has for the past 50 years. Once a circulating flu strain is identified, fertilized hens’ eggs are injected with virus of this strain, either in its wild-type form or in an attenuated form. Large-scale vaccine production requires hundreds of millions of eggs, and weeks of preparation. (However, in 2013 a new eggless vaccine, grown in tanks full of cells instead of hen’s eggs, was approved for people age 18 and older.) Virus for the flu shot is either inactivated or viral bits are collected and purified; attenuated virus is harvested to use in nasal sprays.