| 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 for centuries to come. By the beginning of the 20th 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. A
substance that provokes an immune response is known as an antigen. Weakened microbes,
killed microbes, inactivated toxins, and purified proteins derived from microbes are the
most common antigens used in vaccine development strategies. As science advances,
researchers are developing safer, more effective vaccines that can be delivered in novel
ways (i.e. intranasally).
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 inoculated 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 vaccines have been developed from whole
organisms that have been killed. These inactivated microbes 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.
Subunit Vaccines. Recent research has focused on developing vaccines
that use only part of a 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. Acellular pertussis subunit vaccines
have been demonstrated to be effective in preventing whooping cough in babies and young
children. Vaccine candidates using only the outer polysaccharide (sugar capsules) 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 licensed conjugate vaccines against Haemophilus
influenzae type b (Hib), previously the major cause of bacterial meningitis in
babies and young children, have virtually eliminated the disease in the United States.
Advances in biotechnology are enabling scientists to change the genetic structure of
infectious microbes for use in vaccine development. In these so-called
"recombinant" 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 also 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 inoculated 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 microbes including, including
group A strep, Escherichia coli (E. coli), tuberculosis, and the malaria
parasite Plasmodium falciparum. New genomic sequence data provide important
insights into the components of these organisms that might be incorporated into
candidate vaccines.
NIH, National Institute of Allergy and Infectious Diseases: http://www.nih.gov/niaid
Last Updated: September 2001
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