As an Allergist/Immunologist, I am asked all the time: “how do I boost my immune system?” This is a great question and will be the subject of a number of posts to this blog. Today, in part because of the current highly emotional media coverage of a measles outbreak, the focus will be on vaccination. The scope of this post will be informational: how vaccines were discovered and how vaccines work within the context of the immune system. I hope that good information of this sort will help people make informed decisions about vaccinations for themselves and their families.
The Discovery of Vaccines
The early history of vaccines and vaccination had to do with smallpox. This viral disease is believed to have appeared around 12,000 years ago and led to large-scale epidemics. These epidemics were so severe that they affected the course of history. For example, the first stages of the decline of the Roman Empire, in the year 108 AD, coincided with an epidemic of smallpox that led to the deaths of almost 7 million people. But smallpox was also a continual problem in more recent history. For example, in the 1700s, 400,000 people died every year in Europe of the smallpox. Aside from death, smallpox left disfiguring scars and one third of survivors lost their sight.
The original attempts at prevention of smallpox were called variolation (inoculation). In variolation, a lancet wet with pus taken from someone infected with smallpox was subcutaneously introduced on the arm or leg of a non-immune person. This technique was effective in inducing immunity to smallpox, but 2-3% of variolated people died from the disease, became the source of another smallpox epidemic, or were infected by another disease (such as tuberculosis or syphilis) from the pus used in the variolation.
The incomplete success of variolation led scientifically-minded individuals to begin to consider other methods of preventing smallpox. Such a person was Edward Jenner, the “Father of Vaccination.” He, and others, had observed that dairy maids who can contracted the cowpox were protected from contracting smallpox. On May 14, 1796, Jenner used pus from the cowpox lesions of Sarah Nelms (a dairy maid) to inoculate an 8 year old boy. This boy was later variolated with pus from fresh smallpox lesions and he did not develop smallpox. This is how the vaccine era began. In fact, the term “vaccination” was invented by Jenner and was derived from the Latin words for cow (vacca) and cowpox (vaccinia).
How Vaccines Work
How did the process of injecting pus from sick people into perfectly healthy people work? Why was the pus from smallpox lesions unsafe and the pus from cowpox lesions relatively safe? To understand the answers to these question, it is first important to understand some basics about how the immune system functions. Broadly speaking, we have two types of immunity: innate and adaptive immunity. Innate immunity refers to automatic immunity. Picture a mousetrap. This trap will snap shut, in an automatic way, whenever the cheese in the trap is removed by a mouse. But mice find ways to outsmart the mousetrap and get the cheese, anyway. This is the reason for adaptive immunity. This concept refers to immunity that is learned. In other words, the immune system has components that can learn to fight off specific infections.
In the case of smallpox variolation, the adaptive immune system is exposed to the smallpox virus and, if the recipient of the variolation does not get sick and die, learns to become resistant to future infections with the smallpox virus. Cowpox virus is similar to smallpox virus. In fact, these viruses are so similar that the adaptive immune system, when learning to fight off cowpox virus, simultaneously learns how to fight off smallpox virus. The big advantage, here, is that people don’t get sick or die with the cowpox virus. Therefore, the cowpox virus works in vaccination because it mimics the smallpox virus without causing illness.
Mimicking a real infectious agent without causing illness is the fundamental concept behind every vaccine we have today. Some modern vaccines use viruses that have been killed, and cannot cause infections, but still can allow the adaptive immune system to learn to fight the live virus. Some other vaccines use synthetic analogs of infectious agents, but the concept is all the same.
Influenza virus is an annual challenge, worldwide. Unlike the smallpox virus, which changes little over time, the influenza virus mutates as it spreads. Therefore, every year, people need to be re-vaccinated to protect against new strains. The World Health Organization takes the lead in formulating the components of the influenza vaccine each year. It holds meetings in February, to recommend viruses for inclusion in vaccines for the northern hemisphere, and in September to recommend viruses for inclusion in vaccines for the southern hemisphere. A typical trivalent influenza vaccine will contain strains of influenza A subtype H1N1, influenza A subtype H3N2, and influenza B. In a quadrivalent vaccine, another strain of influenza B is typically added. The selection of the strains of influenza to be used for vaccines is challenging and the match is better in some years than others. The concept used by Edward Jenner with smallpox is exactly the same as that used for influenza vaccine: use an alternative, safer agent to teach the adaptive immune system to protect against the influenza virus, without actually causing the disease. The technology, however, has become very sophisticated and continues to improve. For example, older types of influenza vaccines contain inactivated influenza virus. This is essentially “dead” virus that cannot cause influenza infection but that still contains the important elements to trigger the adaptive immune response. More recently, live attenuated influenza vaccine has become available. This is the well-known “nasal spray flu vaccine” and it contains virus that is live, but has been weakened so that it cannot cause actual influenza. In January, 2013, the United States Food and Drug Administration approved a recombinant influenza vaccine. Influenza viruses are not used at all in the manufacture of this vaccine. Instead, a protein of the influenza virus is made by genetically modifying a virus that infects insect cells, which, in turn, produce this protein. When this protein is used in vaccines, it can teach the adaptive immune system to resist live influenza virus.
Boosting the immune system involves making it stronger. This concept largely has to do with teaching the adaptive part of the immune system to fight off more types of infections. Vaccines, therefore, are a very effective way to boost our immune systems without forcing us to get sick with epidemic infections.
Posted February 7, 2015
Riedel, S. Edward Jenner and the history of smallpox and vaccination. BUMC Proc. 2005; 18:21-25.
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