Immunological Technology. Immunization

Immunization. At the start of the twentieth century, it was known that bacteria and some mysterious filterable agents called viruses could cause infectious diseases, and that people who recovered from a given infection often become specifically immune to that particular infection.

There were only two vaccines known to be useful in preventing human disease, namely the widely used smallpox vaccine and the rarely used rabies vaccine of Louis Pasteur. It had been known for about 10 years that one molecular mechanism of specific immunity is the production of antibody, a protein produced usually in response to a foreign agent and able to bind specifically to that agent.

The smallpox vaccine evolved originally from the cowpox virus, which was used by Edward Jenner to immunize humans in 1796. During serial transmission from human to human, and later from rabbit to rabbit, it evolved into a distinctly different virus now called vaccinia. In the 1970s it played a central role in the first ever global eradication of a human disease: smallpox was officially declared eliminated from the human race in 1979.

Vaccinia was the prototype of many live viral vaccines, whose immunizing effects depend on their being able to cause an infection in the patient, albeit a very mild infection. Other live viral vaccines in common use today include those that immunize against measles, mumps, rubella, polio, varicella, and yellow fever.

These viral vaccines are all said to be attenuated, or of reduced virulence; that is, the infection that they cause is very mild compared with that caused by their wild viral ancestors. Attenuation of infective agents is usually achieved by very simple methods, such as maintaining them for a long time in artificial culture or in an unusual animal host. Most of the attenuated viral vaccines produce strong, long-lasting protective immunity in most people after a single dose.

The only important attenuated bacterial vaccine is the BCG vaccine (Bacille Calmette-Guerin), which is a live, attenuated form of Mycobacterius bovis. It provides about 80 percent protection against tuberculosis in the U.K. but does not provide any demonstrable benefits when used in India.

Some vaccines are created merely by killing the infective agent by exposure to heat, alcohol, formaldehyde, or thiomersal. The usual pertussis (whooping cough) vaccines are of this sort, as is the killed polio vaccine. Others consist of purified single components of the infective agent. Examples are the vaccines against pneumococci, Haemophilus influenzae B, and meningitis C. The important vaccines against tetanus and diphtheria are made by purifying the very potent protein toxins that the bacterial agents produce and then exposing them to formaldehyde, which slightly alters the chemical structure of the toxin, making it nontoxic.

Some pathogens; for example, hepatitis B virus, are difficult to culture in a laboratory, and so the usual methods of creating a vaccine cannot be used. However, if only one protein is important for induction of the immunity, it is usually possible to transfer the gene that codes for it into a yeast or a bacterium that can easily be cultured. The required protein can then be recovered from the cultures and used for immunization. The current hepatitis B vaccine is of this type.

The net effect of vaccines in the twentieth century has been one of the most celebrated success stories of medicine. Beginning with the diphtheria vaccine in the early 1940s, many new vaccines have come into widespread use and the incidence of most childhood infections has fallen about 1000fold. Smallpox has disappeared and polio is also well on its way towards extinction. On the other hand, there are still no affordable and effective vaccines against some of the world’s biggest killers, such as malaria, schistosomiasis, trypanosomiasis, amoebic dysentery, and HIV.