Development
Evolution of Vaccines

Over 200 years ago, English physician Edward Jenner observed that milkmaids stricken with a viral disease called cowpox were rarely victims of a similar disease, smallpox. This observation led to the development of the first vaccine. In an experiment that was to prove a revelation, Jenner took a few drops of fluid from a pustule of a woman who had cowpox and injected the fluid into a healthy young boy who had never had cowpox or smallpox. Six weeks later, Jenner injected the boy with fluid from a smallpox pustule, but the boy remained free of the dreaded smallpox.

In those days, a million people died from smallpox each year in Europe alone, most of them children. Those who survived were often left with grim reminders of their ordeals: blindness, deep scars, and deformities. When Jenner laid the foundation for modern vaccines in 1796, he started on a course that would ease the suffering of people around the world. By the beginning of this century, vaccines for rabies, diphtheria, typhoid fever, and plague were in use, in addition to the vaccine for smallpox. By 1980, an updated version of Jenner=s vaccine led to the total eradication of smallpox.

Since Jenner's time, vaccines have been developed against more than 20 infectious diseases such as influenza, pneumonia, whooping cough, rubella, rabies, meningitis, and hepatitis B. Due to tremendous advances in molecular biology, scientists are using novel approaches to develop vaccines against deadly diseases that still plague humankind.

Scientists use vaccines to trick the human immune system into producing antibodies or immune cells that protect against the real disease-causing organism. Weakened microbes, killed microbes, and inactivated toxins are the most common components used in vaccine development strategies. As science advances, researchers are developing even better ones.

Weakened Microbes. Live microbes are weakened by growing them for many generations in animals or in tissue cultures in the laboratory. These weakened microbes can be innoculated into humans to provide protection from their disease-causing counterparts. The oral polio vaccine, as well as vaccines for mumps, measles, and rubella, have been developed from weakened microbes. Experimental vaccines for influenza and respiratory syncytial virus (RSV) are being tested in clinical trials.

Killed Microbes. A number of other vaccines have been developed from whole organisms that have been killed. These inactivated vaccines do not cause disease in people who receive them, but they can stimulate the immune system. Such vaccines in use today include those against polio and influenza.

Inactivated Toxins. Some bacteria cause disease by producing toxins that invade the bloodstream. Inactivated toxins have been used successfully to prevent diseases such as tetanus and diphtheria since the early 1900s.

Subunit Vaccines. Recent research has focused on developing vaccines that use only part of the bacterium or virus. These vaccines, called subunit vaccines, produce an effective immune response without stirring up separate and potentially harmful immune reactions to the many antigens carried on a microbe. Subunit vaccines are currently available for typhoid, and hepatitis b. An acellular pertussis subunit vaccine has been demonstrated to be effective in preventing whopping cough in babies and young children. Although not considered subunit vaccines, vaccine candidates using only the outer polysaccharide coat of the bacterium have been developed for meningitis and pneumonia.

Conjugate Vaccines. Bacterial diseases such as pneumonia and meningitis once caused considerable illness and death among babies and children in the United States. Bacteria that cause these diseases have an outer coat that cannot be recognized by the immature immune systems of young infants and, therefore, vaccines made from these bacteria are not effective in babies. Researchers have devised a way to produce vaccines that link together proteins or inactivated toxins from a second organism to the outer coat of the bacteria. This enables a baby's immune system to respond to the combined vaccine and produce antibodies, initiating an immune response against the disease-causing organism. The first licensed conjugate vaccine against Haemophilus influenzae type b (Hib), the major cause of bacterial meningitis in babies and young children, has virtually eliminated the disease in the United States.

Vaccines Through Biotechnology

Advances in biotechnology are enabling scientists to change the genetic structure of infectious microbes for use in vaccine development. In these so-called Arecombinant@ vaccines, researchers alter an organism's genetic structure by snipping out a key gene, thereby allowing the organism to produce immunity but not disease. In contrast, researchers can insert a gene into an organism's genetic material, causing it to mass produce "foreign" proteins, or antigens, which can be used to induce an immune response. In another approach, DNA is removed from an organism and modified so that it contains only a fragment of the original genetic material. Scientists theorize that when this "naked" DNA is innoculated into humans, the body's own cells will use it to generate antigens to protect against disease. Such DNA vaccines could potentially result in lifelong protection and are being tested in humans against malaria, influenza, and HIV.

Genome Sequencing. Numerous projects are under way to sequence the genetic instructions, or genomes, of disease-causing microbes. NIH-supported researchers have reported the complete genomic sequence of several agents, including chlamydia, syphilis, tuberculosis, and of the malaria parasite Plasmodium falciparum. The new genomic sequence data provide important insights into the components of these organisms that might be incorporated into candidate vaccines.

Edible Vaccines. In a recent study, researchers found that an edible vaccine could safely and effectively trigger an immune response against the Escherichia coli bacterium, which causes diarrhea. Scientists are now attempting to genetically engineer potatoes, bananas, and tomatoes that, when eaten, will initiate an immune response against harmful intestinal bacteria and viruses.

NIH, National Institute of Allergy and Infectious Diseases:  http://www.niaid.nih.gov/default.htm

This page last modified on February 28, 2000