immunization

immunization Immunization is the process of conferring increased resistance (or decreased susceptibility) to infection. The term ‘vaccination’ is also used to describe this kind of protective measure, although, strictly speaking, this term refers only to the protection conferred against smallpox by material taken from a cow infected with vaccinia virus (which causes cowpox). Inoculation also is used synonymously for immunization, but less commonly nowadays.

The history of immunization goes back to early attempts to prevent smallpox by the Chinese; much later, in the eighteenth century, came the classical experiments of Edward Jenner in Gloucestershire, who induced protection in a child by the inoculation of material from a cow infected with cowpox.

Achievements in the history of immunization are summarized in Table 1. Although the early work to control infection was made before microbiological methods were firmly established, rapid progress was made, based on sound scientific principles, once modern bacteriology, and later virology, came on to the scene. For example, the isolation of poliovirus allowed for the development by Jonas Salk, and later by Albert Sabin in the 1950s, of highly effective poliovaccines, which led to a dramatic diminution in poliomyelitis. Before then, there were alarming outbreaks of this paralytic disease: over 8000 cases occurred in the UK in 1950. By the late 1980s, poliovirus capable of producing paralysis was still circulating widely in all continents of the world except Australia. But by 1998 the Americas were polio-free and elsewhere there is substantial progress being made towards the goal of worldwide eradication of this much dreaded disease.

Similarly, with measles the isolation of measles virus in 1954 made it possible to culture a strain which is now the basis of the measles vaccine in use today. Prior to the use of the vaccine, in the UK as many as 800 000 cases were notified annually, but its introduction has resulted in a dramatic decline.

Table 1 Some important dates in the history of immunization

(?) BC	Early attempts in China to immunize against smallpox
1721	Introduction into Britain from Turkey by Lady Wortley Montagu of inoculation of material
	from smallpox patients into healthy persons (variolation)
1796	First vaccination against smallpox performed by Jenner
1880	Pasteur developed fowl cholera vaccine
1881	Pasteur, Roux, and Chamberland introduced anthrax vaccine
1885	Pasteur developed rabies vaccine
1895	Yersin produced plague vaccine
1898	Almroth Wright developed typhoid vaccine
1921	Calmette and Guérin introduced BCG vaccine
1923	Ramon developed diphtheria toxoid
1927	Ramon and Zoeller developed tetanus toxoid
1940	National immunization campaign launched in Britain by Ministry of Health; did not become
	widespread until 1942
1954	Salk (killed) polio vaccine introduced
1957	Sabin (live) polio vaccine introduced
1960	Measles vaccine developed by Enders
1962	Rubella vaccine developed by Weller
1967	Jeryl Lynn strain of live attenuated mumps vaccine licensed in the US
1968	Meningococcal (type C) vaccine developed
1968	Measles vaccine introduced on a national scale in Britain
1970	Rubella vaccine became available in Britain
1981	Hepatitis B vaccine licensed in US
1988	Measles, Mumps, Rubella (MMR) vaccine introduced into Britain
1992	Haemophilus influenzae b (HiB) vaccine introduced into Britain

Immunization is one of the most cost-effective public health measures available. But although it is possible to manufacture vaccines against a wide variety of viruses and bacteria, it is, of course, important to ensure that the introduction of a particular vaccine will always confer a major benefit to the population receiving it. Therefore certain broad principles are followed before a vaccine is recognized as being suitable for general use: (i) there should be a major risk of contracting the infection against which the vaccine is intended to protect; (ii) the vaccine should prevent an illness which (including complications and sequelae) is regarded as serious and especially if it can be fatal; (iii) the efficacy of the vaccine should be sufficiently high; (iv) any risk associated with the vaccine should be sufficiently low; (v) the procedures and the number of doses required for successful immunization should be acceptable to the public.

An ideal vaccine should confer long-lasting, preferably lifelong, protection against the disease; it should be inexpensive enough for large scale use, stable enough to remain potent during transportation and storage, and have no adverse effect on the recipient. If the introduction of a vaccine is agreed upon at national level then a further decision has to be made as to whether it should be for general use (e.g. polio vaccine) or for specific use when exposure is possible (e.g. typhoid vaccine, given when travelling to regions where typhoid is endemic).

Vaccines may induce immunity against infection either actively or passively.

Active immunization

Active immunization is brought about by stimulating the individual's own immunity by introducing either inactivated (killed) or attenuated (live, but enfeebled) agents (Table 2). The protective response by the body is mainly expressed through: (i) specific antibodies, measurable by serological tests, which confer protection against many agents, particularly viruses and toxins. (ii) the cellular immune response, which involves both phagocytes and ‘memory cells’.

Inactivated vaccines

are prepared in three ways (examples in Table 2): (i) from killed whole organisms; (ii) from sub-units of the killed organisms; (iii) from the toxins which the organisms release, inactivated by formaldehyde (toxoids).

When the organisms have been killed there can be no multiplication within the body, and thus these vaccines cannot produce infection similar to the natural disease. On the other hand, local and whole body reactions may result from response to the organism or to foreign protein used in the vaccine. If the person has not previously been immunized, more than one dose is usually required, although some response can be produced by even a single dose. Protection often lasts for many years, although periodic ‘boosts’ by subsequent injections may be required to maintain immunity.

Attenuated vaccines

are prepared from modified strains of the causal organisms or from related organisms. Because of this, some live vaccines may sometimes cause illness resembling the natural disease, but the symptoms are usually milder. In general, however, these vaccines have fewer side-effects than inactivated ones and the immunity usually lasts for many years.

Passive immunization

Passive immunization is obtained by giving pre-formed, antibodies. These are usually injected in the form of human immunoglobulin or, rarely, antisera prepared in animals. Protection is usually rapid, but the immunity derived is often short-lived, being limited to the time taken for the antibodies to be broken down in the body — from a week or so, with animal antisera, to about six months for protection against hepatitis A by human normal immunoglobulin.

Special risk groups

include those persons particularly liable to suffer from complications of infection, for whom protection by appropriate immunization is therefore of particular importance: for example, those with chronic lung disease, asthma, congenital heart disease, Down's syndrome, or Human Immunodeficiency Virus (HIV) infection, and babies who are born prematurely or are ‘small-for-dates’. Immunization of travellers to some countries overseas is often a particular problem, as the risk of certain infections may be especially high and it often has to be given when time is short.

Surveillance of immunization

procedures is necessary. Immunization it is not without its occasional hazard and it is important that those involved should balance the risk of the disease against the possible risk of the vaccine. Surveillance measures should be aimed at assessing not only the application, utilization, and effectiveness of vaccines in the control of infection, but also any side effects, so that rational decisions about whether to vaccinate can be made.

In conclusion, the achievements of successful immunization policies have been spectacular when the ravages caused by vaccine-preventable infections in former years are compared with those of today. Smallpox has now been eradicated, and other greatly feared infections (such as poliomyelitis) are well under control. Because immunization can often be given quite cheaply and quickly to large numbers of people, it is a remarkably cost-effective measure, which has undoubtedly made a major (if not the major) contribution to the overall protection of the world's population against infection.

Table 2 Examples of viral and bacterial vaccines

	Inactivated (killed)	Toxoids	Attenuated (live)
Viral vaccines	Influenza		Yellow fever
	Poliomyelitis (Salk)		Poliomyelitis (Sabin)
	Hepatitis A		Measles
	Hepatitis B		Rubella
			Mumps
			Rabies
Bacterial vaccines	Typhoid	Diphheria	BCG (tuberculosis)
	Cholera	Tetanus
	Whooping cough

Daniel Reid

Bibliography

Department of Health, Welsh Office, Scottish Home and Health Department (1996). Immunisation against infectious disease. HMSO London.
Nicholl, A. and Rudd, P. (ed.) (1989). British Paediatric Association Manual on infection and immunizations in children. Oxford University Press, Oxford.
Wiedermann, G. and and Jong, E. C. (1997). Vaccine-preventable diseases: principles and practice. In Textbook of travel medicine. B. C. Decker Inc., Hamilton, Ontario.

See also immune response; infectious disease.