Vaccination: An Overview (Parts 1 and 2)

1. How Vaccines Work

 

We live in a world permeated by microorganisms of all kinds – bacteria, fungi, even microscopic animals and plants. Microorganisms interact with human beings in a number of different ways, in many cases seeking us out as their hosts for mutual benefit. Probiotics, for example, are various species of bacteria that live in our intestines, helping us digest our food and absorb nutrients. But some viral and bacterial microorganisms, known as pathogens or germs, cause disease and death in their human hosts rather than coexisting in a mutually beneficial relationship. Vaccination is meant to be a way of protecting us from these pathogens.

Generally speaking, a vaccine is a biological solution, prepared in a laboratory, that contains a weakened or killed virus or bacteria. A person who receives a dose of a vaccine containing a microorganism becomes immune to the disease caused by that microorganism. For example, the measles vaccine grants immunity to the measles virus and thereby to the disease the virus causes. The vaccine accomplishes this by taking advantage of the amazing immune system that exists in the human body.

The immune system is a network of biological processes that combine to protect us from infectious agents such as the pathogens mentioned above. Components of the immune system include physical barriers like skin and mucus but also interior protective agents such as white blood cells and interferons (proteins that protect us from viruses). Our most complex and advanced form of immunity, known as adaptive immunity, involves antibodies (aka immunoglobulins). Antibodies are specific proteins that the immune system produces upon encountering a foreign substance such as a microbe (aka an antigen). An antibody enables the body to more quickly recognize and neutralize the antigen to which it corresponds. As a result, after just one encounter with a pathogen, we can become permanently immune to it upon any future encounters. In other words, due to our ability to produce antibodies, we are able to adapt to an attack such that the same attack won’t work on us twice.

When we are injected with a dose of a vaccine containing a weakened or killed virus or bacteria, the immune system kicks into gear and fights off the pathogen, at the same time producing antibodies against it. Ideally, the pathogen will be weak enough to pose no danger to the body, but strong enough to still stimulate antibody formation. That way, if we encounter the pathogen in the future, we’ll have the antibodies ready to fight it off regardless of its strength. In other words, we’ll be immune to it.

Most vaccines contain, in addition to the pathogen, the following ingredients: animal or human tissues, which serve as a medium in which the pathogen can be cultured; a preservative (such as thiomersal, a mercury-containing compound, or formaldehyde) to keep other pathogens from contaminating the vaccine; a stabilizer such as MSG, to prevent the vaccine from being damaged by heat, light, acidity or humidity; and an “adjuvant,” usually aluminum, which is a substance that increases the response of the immune system. These ingredients, which differ depending on the vaccines, are the result of many decades of research on how to make vaccines safe, effective, and cost-effective.

The most crucial balance to strike in making a vaccine is between a too-strong pathogen and a too-weak one. In the former case, the pathogen may overwhelm the recipient’s immune system, resulting in disease; in the latter case, the pathogen may not stimulate lasting immunity. For example, the oral polio vaccine, which used a live polio virus administered in a similar manner to the way the actual polio virus is contracted, actually caused polio and subsequent paralysis in a small number of children each year before it was discontinued in the early 2000s. For this reason many vaccines are injected, entering the body via the bloodstream, and feature weakened or killed pathogens, relying partially on the afore-mentioned adjuvants for additional stimulation of the immune system. However, this method, presumably because it bypasses certain aspects of the immune system, sometimes does not result in lasting antibody production, in which case it does not confer permanent, lifelong immunity in the subject (hence the need for recurrent “booster shots” of certain vaccines ). In contrast, immunity from a naturally contracted infection is more likely to be permanent, but the risk of serious disease is much greater when acquiring immunity in this way. This dilemma of safety versus effectiveness, of stimulating immunity without harming the patient, has been present since the earliest and most rudimentary attempts at vaccination.

 

2. The History of Vaccination

 

Observing the progress of the Plague of Athens in 430 BC, the Greek historian Thucydides wrote that the plague (now thought to be typhus) “never took any man the second time so as to be mortal.” Those who got sick but survived did not have to fear dying from the disease later on. Similar observations of adaptive immunity may have been what led seventh century Buddhist monks to adopt the practice of drinking a small amount of snake venom to make them immune to the poison from an actual bite. In ancient China, the most threatening disease was smallpox, and by the 10th century one Buddhist nun had found a method for treating smallpox with inoculation. Inoculation, a more general term than vaccination, is the placement of something into a medium in which it can grow and reproduce, such as a plant part grafted on to another plant, or an antigen into a human body. Inoculation with smallpox for immunization purposes is known as variolation.  Over the next few centuries, variolation became common practice in China as a means of providing some protection against smallpox.

Ancient Chinese methods of variolation generally consisted in drying and pulverizing smallpox scabs from people with mild cases of smallpox and blowing the scab powder into the nostrils of healthy people. The mild cases were chosen for the same reason that vaccine makers now often use weakened or killed pathogens: to reduce the risk of inducing a serious infection. Another form of variolation was to have healthy children wear the undergarments of infected children for several days – a tactic similar to the chickenpox playdates of the 20thcentury, prior to the invention of the chickenpox vaccine.

Similar forms of variolation were eventually practiced in India, Byzantium and the Middle East. Due to various causes including the Crusades, the slave trade, and other forms of trade, smallpox spread to Europe and the Americas, and variolation followed.  Variolation techniques now included applying smallpox scab powder to cuts or scratches on the skin, and the process was slowly accepted in the West as a preventative against the disease, though many distrusted it based on its Oriental origin. The major drawback of variolation, however, was that people occasionally developed serious cases of smallpox from the procedure, and either died or suffered scarring and blindness. People sometimes feared the preventative almost as much as the disease itself.

In the eighteenth century, smallpox was widespread throughout England, but one group of people were curiously unaffected by the disease: dairy workers. Through their contact with cows, dairy workers typically became infected with cowpox, a disease similar to smallpox but much less dangerous, which was spread by touch from the infected udders of cows to humans. Cowpox was similar enough to smallpox that the antibodies produced by the infected workers could fight off smallpox microbes as well as cowpox microbes. One of the first people who took advantage of this phenomenon to deliberately induce immunity was an English dairy farmer, Benjamin Jesty.  In the year 1774, during a local smallpox epidemic, Jesty infected his family with the cowpox virus that had already infected his servants and workers. The family easily recovered from the cowpox virus and were untouched by smallpox.

Other farmers carried out similar experiments with success. Eventually, word of this immunization method reached the surgeon and scientist Edward Jenner, who in 1796 decided to test it out by inoculating his gardener’s eight-year-old son with pus from a milkmaid’s cowpox blisters, and then deliberately injecting him with smallpox (scientists had a little more leeway to experiment freely back then).  Since the smallpox virus did not appear to affect the boy, Jenner announced that he had been successfully “vaccinated,” deriving the term fromvacca, Latin for “cow.” Jenner continued to test vaccination on dozens of additional subjects with immediate success, and thanks to his connections in scientific and government circles, was able to widely publicize his findings. He also founded an institution to promote his method, and the British government soon banned variolation in favor of vaccination.

Over the course of the 19th century, vaccination against smallpox became standard practice in most European countries, and was in some cases mandatory. However, smallpox epidemics continued, particularly during times of stress and upheaval.  During the Franco-Prussian war of 1870-72, a smallpox epidemic struck France and Germany and killed over 100,000 people. Jenner himself became aware that both the safety and the effectiveness of the smallpox vaccine were less than ideal. He had discovered that a significant number of people still developed smallpox even after vaccination. They also sometimes became infected with other diseases that had contaminated the vaccine. As for the immunity from vaccination, it generally only lasted 3-5 years and then began to decline.

What Jenner did not know was the nature of smallpox and how it was transmitted. Only by the end of the 19th century did scientists investigating both smallpox and the many other infectious diseases that were prevalent at the time (tuberculosis, diphtheria, cholera and typhus, among others) come up with the famous germ theory of disease. The germ theory stated that each individual infectious disease was caused by an individual, microscopic, living organism. The noted French chemist Louis Pasteur was a major contributor to the theory, having proven that microscopic organisms, good and bad, do not generate spontaneously but reproduce by subsisting on nutrients, and can be airborne or anaerobic. Pasteur subsequently put his discoveries to use in developing pasteurization, the method of heating liquids to kill most microorganisms present within them.

 

The germ theory of disease enabled scientists to more easily develop vaccines against infectious diseases besides smallpox. Pasteur himself worked on vaccines against rabies and anthrax. Aided by his expertise in microbiology, he discovered methods for attenuating (weakening) bacteria in vaccines so that the vaccines could confer immunity with less risk of actually causing disease.  In the following decades, scientists further refined and improved the techniques of vaccine development, introducing vaccines for diphtheria, tetanus, and whooping cough prior to World War II. A polio vaccine was developed during the early 1950s. Since then, vaccines have been developed for many other infectious diseases: measles, mumps, rubella, hepatitis A and B, meningitis, chickenpox, flu and most recently HPV and rotavirus. Today, each disease against which we routinely vaccinate has a small or nonexistent incidence in the developed world. If the 19th century was the Age of Infectious Disease, the 20th century was the Age of the Vaccine.