Vaccine

A vaccine is a medical preparation providing immunity from a vaccine specific disease. Vaccines generally consist of a weakened (attenuated) or killed antigens, associated with a particular disease that are capable of stimulating the body to make specific antibodies to that disease. Vaccines use a variety of different substances ranging from dead microorganisms to genetically engineered antigens to defend the body against potentially harmful microorganisms. Effective vaccines change the immune system by promoting the development of antibodies that can quickly and effectively attack a disease causing microorganism when it enters the body, preventing disease development.

The development of vaccines against diseases ranging from polio and smallpox to tetanus and measles is considered among one of the great accomplishments of medical science. Contemporary researchers are continually attempting to develop new vaccinations against such diseases as Acquired Immune Deficiency Syndrome (AIDS), cancer, influenza, and other diseases.

Physicians have long observed that individuals who were exposed to an infectious disease and survived were somehow protected against that disease in the future. Prior to the invention of vaccines, however, infectious diseases swept through towns, villages, and cities with a horrifying vengeance.

The first effective vaccine was developed against smallpox, an international peril that killed thousands of its victims and left thousands of others permanently disfigured. The disease was so common in ancient China that newborns were not named until they survived the disease. The development of the vaccine in the late 1700s followed centuries of innovative efforts to fight smallpox.

The ancient Chinese were the first to develop an effective measure against smallpox. A snuff made from powdered smallpox scabs 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.

By the late 1600s, some 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 into the skin to obtain immunity. At the time, conventional medical doctors in Europe relied solely on isolation and quarantine of people with the disease.

Changes in these practices took place, in part, through the vigorous effort of Lady Mary Wortley Montague, the wife of the British ambassador to Turkey in the early 1700s. Montague said the Turks injected a preparation of smallpox scabs into the veins of susceptible individuals. Those injected generally developed a mild case of smallpox from which they recovered rapidly, Montague wrote.

Upon her return to Great Britain, Montague helped convince King George I to allow trials of the technique on inmates in Newgate Prison. Success of the trials cleared the way for variolation, or the direct injection of smallpox, to become accepted medical practice in England until a vaccination was developed later in the century. Variolation also was credited with protecting United States soldiers from smallpox during the Revolutionary War.

Doubts remained about the practice. Individuals were known to die after receiving the smallpox injections.

The next leap in the battle against smallpox occurred when Edward Jenner (1749–1823) acted on a hunch. Jenner, a country physician and an orphan since the age of five, observed that people who were in contact with cows often developed cowpox, which caused pox but was not life threatening. Those people did not develop smallpox. In 1796, Jenner decided to test his hypothesis that cowpox could be used to protect humans against smallpox. Jenner 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.

Jenner's discovery launched a new era in medicine, one in which the intricacies of the immune system would become increasingly important. Contemporary knowledge suggests that cowpox was similar enough to smallpox that the antigen included in the vaccine stimulated an immune response to smallpox. Exposure to cowpox antigen transformed the boy's immune system, generating cells that would remember the original antigen. The smallpox vaccine, like the many others that would follow, carved a protective pattern in the immune system, one that conditioned the immune system to move faster and more efficiently against future infection by smallpox.

The term vaccination, taken from the Latin for cow (vacca) was developed by Louis Pasteur (1822–1895) a century later to define Jenner's discovery. The term also drew from the word vaccinia, the virus drawn from cowpox and developed in the laboratory for use in the smallpox vaccine. In spite of Jenner's successful report, critics questioned the wisdom of using the vaccine, with some worrying that people injected with cowpox would develop animal characteristics, such as women growing animal hair. Nonetheless, the vaccine gained popularity, and replaced the more risky direct inoculation with smallpox. In 1979, following a major cooperative effort between nations and several international organizations, world health authorities declared smallpox the only infectious disease to be completely eliminated.

The concerns expressed by Jenner's contemporaries about the side effects of vaccines would continue to follow the pioneers of vaccine development. Virtually all vaccinations continue to have side effects, with some of these effects due to the inherent nature of the vaccine, some due to the potential for impurities in a manufactured product, and some due to the potential for human error in administering the vaccine.

Virtually all vaccines would also continue to attract intense public interest. This was demonstrated in 1885 when 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.

Until development of the rabies vaccine, Pasteur had been criticized by the public, though his great discoveries included the development of the food preservation process called pasteurization. With the discovery of a rabies vaccine, Pasteur became an honored figure. In France, his birthday declared a national holiday, and streets renamed after him.

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.

The story of the most celebrated vaccine in modern times, the polio vaccine, is one of discovery and revision. While the viruses that cause polio appear to have been present for centuries, the disease emerged to an unusual extent in the early 1900s. At the peak of the epidemic, in 1952, polio killed 3,000 Americans and 58,000 new cases of polio were reported. The crippling disease caused an epidemic of fear and illness as Americans—and the world—searched for an explanation of how the disease worked and how to protect their families.

The creation of a vaccine for poliomyelitis by Jonas Salk (1914–1995) in 1955 concluded decades of a drive to find a cure. The Salk vaccine, a killed virus type, contained the three types of polio virus which had been identified in the 1940s.

In 1955, the first year the vaccine was distributed, disaster struck. Dozens of cases were reported in individuals who had received the vaccine or had contact with individuals who had been vaccinated. The culprit was 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.

Production problems with the Salk vaccine were overcome following the 1955 disaster. Then in 1961, an oral polio vaccine developed by Albert B. Sabin (1906–1993) was licensed in the United States. The continuing controversy over the virtues of the Sabin and Salk vaccines is a reminder of the many complexities in evaluating the risks versus the benefits of vaccines.

The Sabin vaccine, which used weakened, live polio virus, 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. Though polio has not been completely eradicated, there were only 144 confirmed cases worldwide in 1999.

Effective vaccines have limited many of the life-threatening infectious diseases. In the United States, children starting kindergarten are required to be immunized against polio, diphtheria, tetanus, and several other diseases. Other vaccinations are used only by populations at risk, individuals exposed to disease, or when exposure to a disease is likely to occur due to travel to an area where the disease is common. These include influenza, yellow fever, typhoid, cholera, and hepatitis A and B.

The influenza virus is one of the more problematic diseases because the viruses constantly change, making development of vaccines difficult. 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.

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 uses bacterial polysaccharides, carbohydrates found in bacteria which contain large numbers of monosaccharides, a simple sugar. These classical methods 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. To mitigate dangers of side effects, researchers and clinicians are preparing vaccines that consist of synthetic peptides representing only a small part of the antigen present in the enitrre organism are currently in development.

As medical knowledge has increased—particularly in the field of DNA vaccines—researchers have set their sights on a wealth of possible new vaccines for cancer, melanoma, AIDS, influenza, and numerous others. 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 socalled "naked DNA." Microscopic portions of a viruses' 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.

Since the emergence of AIDS in the early 1980s, a worldwide search against the disease has resulted in clinical trials for more than 25 experimental vaccines. 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 June 2002, a proven vaccine for AIDS had not yet been proven in clinical trials.

Stimulating the immune system is also 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 other areas. 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 be efficient travelers in the body, as carriers of vaccine antigens. Such bacteria or viruses would be treated or engineered to make them incapable of causing illness.

Current research also focuses on developing better vaccines. The Children's Vaccine Initiative, supported by the World Health Organization, the United Nation's Children's Fund, and other organizations, are working diligently to make vaccines easier to distribute in developing countries. Although more than 80% of the world's children were immunized by 1990, no new vaccines have been introduced extensively since then. More than four million people, mostly children, die needlessly every year from preventable diseases. Annually, measles kills 1.1 million children worldwide; whooping cough (pertussis) kills 350,000; hepatitis B 800,000; Haemophilus influenzae type b (Hib) 500,000; tetanus 500,000; rubella 300,000; and yellow fever 30,000. Another eight million die from diseases for which vaccines are still being developed. These include pneumococcal pneumonia (1.2 million); acute respiratory virus infections (400,000), malaria (two million); AIDS (2.3 million); and rotavirus (800,000). In August, 1998, the Food and Drug Administration approved the first vaccine to prevent rotavirus—a severe diarrhea and vomiting infection.

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 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.

This outbreak reflected the limited reach of vaccination programs. Only 15% of the children between the ages of 16 and 59 months who developed measles between 1989 and 1991 had received the recommended measles vaccination. In many cases parent's erroneously reasoned that they could avoid even the minimal risk of vaccine side effects "because all other children were vaccinated."

Nearly all children are immunized properly by the time they start school. However, very young children are far less likely to receive the proper vaccinations. Problems behind the lack of immunization range from the limited health care received by many Americans to the increasing cost of vaccinations. Health experts also contend that keeping up with a vaccine schedule, which requires repeated visits, may be too challenging for Americans who do not have a regular doctor or health provider.

Internationally, the challenge of vaccinating large numbers of people has also proven to be immense. Also, the reluctance of some parents to vaccinate their children due to potential side effects has limited vaccination use. Parents in the United States and several European countries have balked at vaccinating their children with the pertussis vaccine due to the development of neurological complications in a small number of children given the vaccine. Because of incomplete immunization, whooping cough remains common in the United States, with 30,000 cases and about 25 deaths due to complications annually. One response to such concerns has been testing in the United States of a new pertussis vaccine that has fewer side effects.

Researchers look to genetic engineering, gene discovery, and other innovative technologies to produce new vaccines.