Investigations of the circumstances surrounding an illness outbreak can be a valuable means of determining how an infection is spread, its natural reservoirs, and in identifying subpopulations that display immunity to the infection. These forensic investigations can aid in the development of protective measures. Principle among protective measures are vaccines.
A vaccine is a medical preparation given to a person to provide immunity from a disease. Vaccines use a variety of different substances ranging from dead microorganisms to genetically engineered antigens to defend the body against potentially harmful antigens. Effective vaccines change the immune system by promoting the development of antibodies that can quickly and effectively attack disease causing microorganisms or viruses when they enter the body, preventing disease development.
The development of vaccines against diseases including polio, smallpox, tetanus, and measles is considered among the great accomplishments of medical science. Researchers are continually attempting to develop new vaccinations against other diseases. In particular, vigorous research into vaccines for acquired immune deficiency syndrome (AIDS), some cancer, severe acute respiratory syndrome (SARS), and avian influenza is currently underway.
The first successful vaccine was developed from cowpox as a treatment for smallpox. Coined by Louis Pasteur (1822–1895), the etymology of the term vaccine reflects this achievement. It is taken from the Latin for cow (vacca) and the word vaccinia, the virus that causes cowpox.
This first effective vaccine developed treated smallpox, a virulent disease that killed thousands of its victims and left thousands of others disfigured. In one of the first forms of inoculation, ancient Chinese people developed a snuff made from powdered smallpox scabs that was blown into the nostrils of uninfected individuals. Some individuals died from the therapy; however, in most cases, the mild infection produced offered protection from later, more serious infection.
In the late 1600s, European peasants employed a similar method of immunizing themselves against smallpox. In a practice referred to as "buying the smallpox," peasants in Poland, Scotland, and Denmark reportedly injected the smallpox virus under the skin to obtain immunity.
Lady Mary Wortley Montagu, the wife of the British ambassador to Turkey, brought information on immunization back to Europe in the early 1700s. Montague reported that the Turks injected a preparation of small pox scabs into the veins of susceptible individuals. Those injected generally developed a mild case of smallpox from which they recovered rapidly. Montague convinced King George I to allow trials of the technique on inmates in Newgate Prison. Although some individuals died after receiving the injections, the trials were successful enough that variolation, or the direct injection of smallpox, became Page 712 | Top of Article accepted medical practice. Variolation also was credited with protecting United States soldiers from smallpox during the Revolutionary War.
Edward Jenner (1749–1823), an English country physician, observed that people who were in contact with cows often developed cowpox, which caused pox sores but was not life threatening. Those people never developed smallpox. In 1796 Jenner tested the hypothesis that cowpox could be used to protect humans against smallpox. He injected a healthy eight-year-old boy with cowpox obtained from a milkmaid's sore. The boy was moderately ill and recovered. Jenner then injected the boy twice with the smallpox virus, and the boy did not get sick.
Modern knowledge of the immune system suggests that the virus that causes cowpox is similar enough to the virus that causes smallpox that the vaccine simulated an immune response to smallpox. Exposure to cowpox antigen stimulated the boy's immune system, producing cells that attacked the original antigen as well as the smallpox antigen. The vaccine also conditioned the immune system to produce antibodies more quickly and more efficiently against future infection by smallpox.
During the two centuries since its development, the smallpox vaccine gained popularity, protecting millions from contracting the disease. In 1979, following a major cooperative effort between nations and several international organizations, world health authorities declared smallpox the only infectious disease to be eradicated from the planet.
In 1885 Louis Pasteur (1822–1895) saved the life of Joseph Meister, a nine year old who had been attacked by a rabid dog. Pasteur's series of experimental rabies vaccinations on the boy proved the effectiveness of the new vaccine.
Pasteur's rabies vaccine, the first human vaccine created in a laboratory, was made of an extract gathered from the spinal cords of rabies-infected rabbits. The live virus was weakened by drying over potash. The new vaccination was far from perfect, causing occasional fatalities and temporary paralysis. Individuals had to be injected 14 to 21 times.
The rabies vaccine has been refined many times. In the 1950s, a vaccine grown in duck embryos replaced the use of live virus, and in 1980, a vaccine developed in cultured human cells was produced. In 1998, the newest vaccine technology—genetically engineered vaccines—was applied to rabies. The new DNA vaccine cost a fraction of the regular vaccine. While only a few people die of rabies each year in the United States, more than 40,000 die worldwide, particularly in Asia and Africa. The less expensive vaccine will make vaccination far more available to people in less developed nations.
In the early 1900s polio was extremely virulent in the United States. At the peak of the epidemic, in 1952, polio killed 3,000 Americans, and 58,000 new cases of polio were reported.
In 1955 Jonas Salk (1914–1995) developed a vaccine for poliomyelitis. The Salk vaccine, a killed virus type, contained the three types of poliovirus that had been identified in the 1940s. In the first year the vaccine was distributed, dozens of cases of polio were reported in individuals who had received the vaccine or had contact with individuals who had been vaccinated. This resulted from an impure batch of vaccine that had not been completely inactivated. By the end of the incident, more than 200 cases had developed and 11 people had died.
In 1961, an oral polio vaccine developed by Albert B. Sabin (1906–1993) was licensed in the United States. The Sabin vaccine, which uses weakened, live polio viruses, quickly overtook the Salk vaccine in popularity in the United States, and is currently administered to all healthy children. Because it is taken orally, the Sabin vaccine is more convenient and less expensive to administer than the Salk vaccine.
Advocates of the Salk vaccine, which is still used extensively in Canada and many other countries, contend that it is safer than the Sabin oral vaccine. No individuals have developed polio from the Salk vaccine since the 1955 incident. In contrast, the Sabin vaccine has a very small, but significant, rate of complications, including the development of polio. However, there has not been one new case of polio in the United States since 1975, or in the Western Hemisphere since 1991. Although polio has not been completely eradicated, there were only 144 confirmed cases worldwide in 1999.
Developing a vaccine against the influenza virus is problematic because the viruses that cause the flu constantly evolve. Scientists grapple with predicting what particular influenza strain will predominate in a given year. When the prediction is accurate, the vaccine is effective. When they are not, the vaccine is often of little help. However, the flu shot has had enough success that pediatricians are now recommending the vaccine for children older than six months.
Since the emergence of AIDS in the early 1980s, research for a treatment for the disease has resulted in clinical trials for more than 25 experimental vaccines. Page 713 | Top of Article These range from whole-inactivated viruses to genetically engineered types. Some have focused on a therapeutic approach to help infected individuals to fend off further illness by stimulating components of the immune system. Others have genetically engineered a protein on the surface of HIV to prompt immune response against the virus; and yet others attempted to protect uninfected individuals. The challenges in developing a protective vaccine include the fact that HIV appears to have multiple viral strains and mutates quickly.
In January, 1999, a promising study was reported in Science magazine of a new AIDS vaccine created by injecting a healthy cell with DNA from a protein in the AIDS virus that is involved in the infection process. This cell was then injected with genetic material from cells involved in the immune response. Once injected into the individual, this vaccine "catches the AIDS virus in the act," exposing it to the immune system and triggering an immune response. This discovery offers considerable hope for development of an effective vaccine. As of 2005, a vaccine for AIDS had not been proven in clinical trials.
Stimulating the immune system is considered key by many researchers seeking a vaccine for cancer. Currently numerous clinical trials for cancer vaccines are in progress, with researchers developing experimental vaccines against cancer of the breast, colon, and lung, among others. Promising studies of vaccines made from the patient's own tumor cells and genetically engineered vaccines have been reported. Other experimental techniques attempt to penetrate the body in ways that could stimulate vigorous immune responses. These include using bacteria or viruses, both known to efficiently circulate through the body, as carriers of vaccine antigens. These bacteria or viruses could be treated or engineered to make them incapable of causing illness.
The classic methods for producing vaccines use biological products obtained directly from a virus or a bacteria. Depending on the vaccination, the virus or bacteria is either used in a weakened form, as in the Sabin oral polio vaccine; killed, as in the Salk polio vaccine; or taken apart so that a piece of the microorganism can be used. For example, the vaccine for Streptococcus pneumoniae, which causes pneumonia, uses bacterial polysaccharides, carbohydrates found in bacteria which contain large numbers of monosaccharides, a simple sugar. The different methods for producing vaccines vary in safety and efficiency. In general, vaccines that use live bacterial or viral products are extremely effective when they work, but carry a greater risk of causing disease. This is most threatening to individuals whose immune systems are weakened, such as individuals with leukemia. Children with leukemia are advised not to take the oral polio vaccine because they are at greater risk of developing the disease. Vaccines which do not include a live virus or bacteria tend to be safer, but their protection may not be as great.
The classical types of vaccines are all limited in their dependence on biological products, which often must be kept cold, may have a limited life, and can be difficult to produce. The development of recombinant vaccines—those using chromosomal parts (or DNA) from a different organism—has generated hope for a new generation of man-made vaccines. The hepatitis B vaccine, one of the first recombinant vaccines to be approved for human use, is made using recombinant yeast cells genetically engineered to include the gene coding for the hepatitis B antigen. Because the vaccine contains the antigen, it is capable of stimulating antibody production against hepatitis B without the risk that live hepatitis B vaccine carries by introducing the virus into the blood stream.
As medical knowledge has increased—particularly in the field of DNA vaccines—researchers are working toward developing new vaccines for cancer, melanoma, AIDS, influenza, and numerous others illnesses. Since 1980, many improved vaccines have been approved, including several genetically engineered (recombinant) types which first developed during an experiment in 1990. These recombinant vaccines involve the use of so-called "naked DNA." Microscopic portions of a viruses's DNA are injected into the patient. The patient's own cells then adopt that DNA, which is then duplicated when the cell divides, becoming part of each new cell. Researchers have reported success using this method in laboratory trials against influenza and malaria. These DNA vaccines work from inside the cell, not just from the cell's surface, as other vaccines do, allowing a stronger cell-mediated fight against the disease. Also, because the influenza virus constantly changes its surface proteins, the immune system or vaccines cannot change quickly enough to fight each new strain. However, DNA vaccines work on a core protein, which researchers believe should not be affected by these surface changes.
The measles epidemic of 1989 was a graphic display of the failure of many Americans to be properly immunized. A total of 18,000 people were infected, including 41 children who died after developing measles, an infectious, viral illness whose complications include pneumonia and encephalitis. The Page 714 | Top of Article epidemic was particularly troubling because an effective, safe vaccine against measles has been widely distributed in the United States since the late 1960s. By 1991, the number of new measles cases had started to decrease, but health officials warned that measles remained a threat.