VACCINE

suspension of weakened, killed, or fragmented microorganisms or toxins or of antibodies or lymphocytes that is administered primarily to prevent disease. A vaccine can confer active immunity against a specific harmful agent by stimulating the immune system to attack the agent. Once stimulated by a vaccine, the antibody-producing cells, called B lymphocytes, remain sensitized and ready to respond to the agent should it ever gain entry to the body. A vaccine may also confer passive immunity by providing antibodies or lymphocytes already made by an animal or human donor. Vaccines are usually administered by injection (parenteral administration), but some are given orally. Vaccines applied to mucosal surfaces, such as those lining the gut or nasal passages, seem to stimulate a greater antibody response and may be the most effective route of administration. Vaccination against smallpox, after a painting by Constant Desbordes circa 1820. The discovery of vaccination is attributed to the British physician Edward Jenner, who in 1796 used the cowpox virus (vaccinia) to confer protection against smallpox, a related virus, in humans. Prior to this use, however, the principle of vaccination was applied by Asian physicians who gave children dried crusts from the lesions of people suffering from smallpox to protect against the disease. While some developed immunity, others developed the disease. Jenner's contribution was to use a substance similar to, but safer than, smallpox to confer immunity. He thus exploited the relatively rare situation in which immunity to one virus confers protection against another viral disease. In 1881 the French microbiologist Louis Pasteur demonstrated immunization against anthrax by injecting sheep with a preparation containing attenuated forms of the bacillus that causes the disease. Four years later he developed a protective suspension against rabies. In the United States, mass vaccination programs carried out against diphtheria, polio, and measles Since Pasteur's time, a widespread and intensive search for new vaccines has been conducted, and vaccines against both bacteria and viruses are produced, as well as vaccines against venoms and other toxins. Through vaccination, smallpox has been eradicated worldwide, and polio much reduced. Vaccines have also been developed for mumps, measles, typhoid, cholera, plague, tuberculosis, tularemia, pneumococcal infection, tetanus, influenza, yellow fever, hepatitis A and B, some types of encephalitis, and typhusalthough some of these vaccines are less than 100 percent effective or are used only in selected population groups at high risk. Interest in bacterial vaccines slackened with the introduction of antibiotics in the mid-20th century, but vaccines remain a mainstay in the fight against many infectious diseases, especially viral infections, which do not generally respond to antibiotics. The challenge in vaccine development consists in devising a vaccine strong enough to ward off infection without making the individual seriously ill. To this end, investigators have devised different types of vaccines. Weakened, or attenuated, vaccines consist of microorganisms that have lost the ability to cause serious illness but retain the ability to stimulate immunity. They may produce a mild or subclinical form of the disease. Attenuated vaccines include those for measles, mumps, polio (the Sabin vaccine), rubella, and tuberculosis. Inactivated vaccines are those that contain organisms that have been killed or inactivated with heat or chemicals. These, too, elicit an immune response, but the response often is less complete. Because inactivated vaccines are not as effective at fighting infection as those made from attenuated microorganisms, greater quantities of inactivated vaccines are administered. Vaccines against rabies, polio (the Salk vaccine), some forms of influenza, and cholera are made from inactivated microorganisms. Another type is a subunit vaccine, which is made from proteins found on the surface of infectious agents. Vaccines for influenza and hepatitis B are of this type. When toxins, the metabolic by-products of infectious organisms, are inactivated to form toxoids, they can be used to stimulate immunity against tetanus, diphtheria, and whooping cough. In the late 20th century, advances in laboratory techniques allowed approaches to vaccine development to be refined. Medical researchers could identify the genes of a pathogen (disease-causing microorganism) that encode the protein or proteins that stimulate the immune response to that organism. This has allowed the immunity-stimulating proteins (called antigens) to be mass-produced and used in vaccines. It also has made it possible to alter pathogens genetically and produce weakened strains of viruses. In this way, harmful proteins from pathogens can be deleted or modified, thus providing a safer and more effective method by which to manufacture attenuated vaccines. Recombinant DNA technology has also proved useful in developing vaccines to viruses that cannot be grown successfully or that are inherently dangerous. Genetic material that codes for a desired antigen is inserted into the attenuated form of a large virus, such as the vaccinia virus, which carries the foreign genes piggyback. The altered virus is injected into an individual to stimulate antibody production to the foreign proteins and thus confer immunity. This approach potentially enables the vaccinia virus to function as a live vaccine against several diseases, once it has received genes derived from the relevant disease-causing microorganisms. A similar procedure can be followed using a modified bacterium, such as Salmonella typhimurium, as the carrier of a foreign gene. Another approach, called naked DNA therapy, involves injecting DNA that encodes a foreign protein into muscle cells. These cells produce the foreign antigen, which stimulates an immune response. (For further information, see the article immunization.)