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Child receiving an oral polio vaccine
ICD-9-CM 99.3-99.5


The active agent of a vaccine may be intact but inactivated (non-infective) or attenuated (with reduced infectivity) forms of the causative pathogens, or purified components of the pathogen that have been found to be highly immunogenic (e.g., outer coat proteins of a virus). Toxoids are produced for immunization against toxin-based diseases, such as the modification of tetanospasmin toxin of tetanus to remove its toxic effect but retain its immunogenic effect.[5]

Smallpox was probably the first disease people tried to prevent by purposely inoculating themselves with other infections[6][7] and was the first disease for which a vaccine was produced. The smallpox vaccine was designed in 1796 by the British physician Edward Jenner, although at least six people had used the same principles several years earlier.[8] Louis Pasteur furthered the concept through his pioneering work in microbiology. The immunization was called vaccination because it was derived from a virus affecting cows (Latin: vacca—cow).[6][8] Smallpox was a contagious and deadly disease, causing the deaths of 20–60% of infected adults and over 80% of infected children.[9] When smallpox was finally eradicated in 1979, it had already killed an estimated 300–500 million people[10][11][12] during the 20th century alone.

In common speech, 'vaccination' and 'immunization' have a similar meaning. This distinguishes it from inoculation, which uses unweakened live pathogens, although in common usage either is used to refer to an immunization. Vaccination efforts have been met with some controversy since their inception, on scientific, ethical, political, medical safety, and religious grounds. In rare cases, vaccinations can injure people and, in the United States, they may receive compensation for those injuries under the National Vaccine Injury Compensation Program. Early success and compulsion brought widespread acceptance, and mass vaccination campaigns have greatly reduced the incidence of many diseases in numerous geographic regions.

Mechanism of function[edit]

Generically, the process of artificial induction of immunity, in an effort to protect against infectious disease, works by 'priming' the immune system with an 'immunogen'. Stimulating immune responses with an infectious agent is known as immunization. Vaccination includes various ways of administering immunogens.

Polio vaccination started in Sweden in 1957.

Some vaccines are administered after the patient already has contracted a disease. Vaccinia given after exposure to smallpox, within the first three days, is reported to attenuate the disease considerably, and vaccination up to a week after exposure probably offers some protection from disease or may modify the severity of disease.[13] The first rabies immunization was given by Louis Pasteur to a child after he was bitten by a rabid dog. Subsequent to this, it has been found that, in people with uncompromised immune systems, four doses of rabies vaccine over 14 days, wound care, and treatment of the bite with rabies immune globulin, commenced as soon as possible after exposure, is effective in preventing the development of rabies in humans.[14] Other examples include experimental AIDS, cancer and Alzheimer's disease vaccines. Such immunizations aim to trigger an immune response more rapidly and with less harm than natural infection.

Most vaccines are given by hypodermic injection as they are not absorbed reliably through the intestines. Live attenuated polio, some typhoid and some cholera vaccines are given orally to produce immunity in the bowel.

Adjuvants and preservatives[edit]



Vaccines may also contain preservatives to prevent contamination with bacteria or fungi. Until recent years, the preservative thimerosal was used in many vaccines that did not contain live virus. As of 2005, the only childhood vaccine in the U.S. that contains thimerosal in greater than trace amounts is the influenza vaccine,[1] which is currently recommended only for children with certain risk factors.[15] Single-dose Influenza vaccines supplied in the UK do not list Thiomersal (its UK name) in the ingredients. Preservatives may be used at various stages of production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.[16][dead link]

Vaccination versus inoculation[edit]

Many times these words are used interchangeably, as if they were synonyms. In fact, they are different things. As doctor Byron Plant explains: "Vaccination is the more commonly used term, which actually consists of a 'safe' injection of a sample taken from a cow suffering from cowpox... Inoculation, a practice probably as old as the disease itself, is the injection of the variola virus taken from a pustule or scab of a smallpox sufferer into the superficial layers of the skin, commonly on the upper arm of the subject. Often inoculation was done 'arm to arm' or less effectively 'scab to arm'..."[17]

Vaccination began in the 18th century with the work of Edward Jenner.[18][19][20]


Vaccines work by presenting a foreign antigen to the immune system to evoke an immune response, but there are several ways to do this. Four main types are currently in clinical use:

  1. An inactivated vaccine consists of virus or bacteria that are grown in culture and then killed using a method such as heat or formaldehyde. Although the virus or bacteria particles are destroyed and cannot replicate, the virus capsid proteins or bacterial wall are intact enough to be recognized and remembered by the immune system and evoke a response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. Since the properly produced vaccine does not reproduce, booster shots are required periodically to reinforce the immune response.
  2. In an attenuated vaccine, live virus or bacteria with very low virulence are administered. They will replicate, but locally or very slowly. Since they do reproduce and continue to present antigen to the immune system beyond the initial vaccination, boosters may be required less often. These vaccines may be produced by passaging, for example, adapting a virus into different host cell cultures, such as in animals, or at suboptimal temperatures, allowing selection of less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence, which is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals. Reversions of virulence were described for a few attenuated viruses of chickens (infectious bursal disease virus, avian infectious bronchitis virus, avian infectious laryngotracheitis virus [2], avian metapneumovirus [3])[21]
  4. A subunit vaccine presents an antigen to the immune system without introducing viral particles, whole or otherwise. One method of production involves isolation of a specific protein from a virus or bacterium (such as a bacterial toxin) and administering this by itself. A weakness of this technique is that isolated proteins may have a different three-dimensional structure than the protein in its normal context, and will induce antibodies that may not recognize the infectious organism. In addition, subunit vaccines often elicit weaker antibody responses than the other classes of vaccines.

A number of other vaccine strategies are under experimental investigation. These include DNA vaccination and recombinant viral vectors.


In written history[edit]

Jenner's handwritten draft of the first vaccination.

It is believed likely that some form of inoculation was developed in India or China before the 16th century.[6] Scholar Ole Lund comments: "The earliest documented examples of vaccination are from India and China in the 17th century, where vaccination with powdered scabs from people infected with smallpox was used to protect against the disease. Smallpox used to be a common disease throughout the world and 20% to 30% of infected persons died from the disease. Smallpox was responsible for 8% to 20% of all deaths in several European countries in the 18th century. The tradition of inoculation may have originated in India in 1000 BCE."[22] The mention of inoculation in the Sact'eya Grantham, an Ayurvedic text, was noted by the French scholar Henri Marie Husson in the journal Dictionaire des sciences médicales.[23] Almroth Wright, the professor of pathology at Netley, further helped shape the future of vaccination by conducting limited experiments on the professional staff at Netly, including himself. The outcome of these experiments resulted in further development of vaccination in Europe.[24] The Anatolian Ottoman Turks knew about methods of inoculation. This kind of inoculation and other forms of variolation were introduced into England by Lady Montagu, a famous English letter-writer and wife of the English ambassador at Istanbul between 1716 and 1718, who almost died from smallpox as a young adult and was physically scarred from it. She came across the Turkish methods of inoculation, consenting to have her son inoculated by the Embassy surgeon Charles Maitland in the Turkish way. Lady Montagu wrote to her sister and friends in England describing the process in details. On her return to England she continued to propagate the Turkish tradition of inoculation and had many of her relatives inoculated. The breakthrough came when a scientific description of the inoculation operation was submitted to the Royal Society in 1724 by Dr Emmanual Timoni, who had been the Montagu's family physician in Istanbul. Inoculation was adopted both in England and in France nearly half a century before Jenner's famous smallpox vaccine of 1796.[25]

Since then vaccination campaigns have spread throughout the globe, sometimes prescribed by law or regulations (See Vaccination Acts). Vaccines are now used against a wide variety of diseases besides smallpox. Louis Pasteur further developed the technique during the 19th century, extending its use to killed agents protecting against anthrax and rabies. The method Pasteur used entailed treating the agents for those diseases so they lost the ability to infect, whereas inoculation was the hopeful selection of a less virulent form of the disease, and Jenner's vaccination entailed the substitution of a different and less dangerous disease for the one protected against. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery.

A doctor performing a typhoid vaccination in Texas, 1943.

Prior to vaccination with cowpox, the only known protection against smallpox was inoculation or variolation (Variola - the Smallpox viruses) where a small amount of live smallpox virus was administered to the patient; this carried the serious risk that the patient would be killed or seriously ill. The death rate from variolation was reported to be around a tenth of that from natural infection with Variola, and the immunity provided was considered quite reliable. Factors contributing to the efficacy of variolation probably include the choices of Variola Minor strains used, the relatively low number of cells infected in the first phase of multiplication following initial exposure, and the exposure route used, via the skin or nasal lining rather than inhalation of droplets into the lungs.

Consistency would suggest the activity should have predated Jenner's description of an effective vaccination system, and there is some history relating to opposition to the older and more hazardous procedure of variolation.[26] In modern times, the first vaccine-preventable disease targeted for eradication was smallpox. The World Health Organization (WHO) coordinated the global effort to eradicate this disease. The last naturally occurring case of smallpox occurred in Somalia in 1977.

Maurice Hilleman was the most prolific of inventors of vaccines. He developed successful vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and Haemophilus influenzae bacteria.[27]

In 1988, the governing body of WHO targeted polio for eradication by 2000. Although the target was missed, eradication is very close. The next eradication target would most likely be measles, which has declined since the introduction of measles vaccination in 1963.

In 2000, the Global Alliance for Vaccines and Immunization was established to strengthen routine vaccinations and introduce new and under-used vaccines in countries with a per capita GDP of under US$1000. GAVI is now entering its second phase of funding, which extends through 2014.

Society and culture[edit]

Poster for vaccination against smallpox.

In an attempt to eliminate the risk of outbreaks of some diseases, at various times several governments and other institutions have instituted policies requiring vaccination for all people. For example, an 1853 law required universal vaccination against smallpox in England and Wales, with fines levied on people who did not comply. Common contemporary U.S. vaccination policies require that children receive common vaccinations before entering public school.

Beginning with early vaccination in the nineteenth century, these policies were resisted by a variety of groups, collectively called anti-vaccinationists, who object on scientific, ethical, political, medical safety, religious, and other grounds. Common objections are that vaccinations do not work, that compulsory vaccination represents excessive government intervention in personal matters, or that the proposed vaccinations are not sufficiently safe.[28] Many modern vaccination policies allow exemptions for people who have compromised immune systems, allergies to the components used in vaccinations or strongly held objections.[29]

In countries with limited financial resources, limited coverage is a major problem causing unnecessary morbidity and mortality.[30] More affluent countries are able to subsidize vaccinations for at-risk groups, resulting in more comprehensive and effective cover. In Australia, for example, the Government subsidizes vaccinations for seniors and indigenous Australians.[31]

Public Health Law Research,[32] an independent organization, reported in 2009 that there is insufficient evidence to assess the effectiveness of requiring vaccinations as a condition for specified jobs as a means of reducing incidence of specific diseases among particularly vulnerable populations;[33] that there is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools.;[34] and that there is strong evidence supporting the effectiveness of standing orders, which allow healthcare workers without prescription authority to administer vaccine as a public health intervention aimed at increasing vaccination rates.[35]

Vaccination-autism controversy[edit]

One of the most noteworthy allegations of vaccine-induced injury is the MMR vaccine controversy. A fraudulent 1998 paper by Andrew Wakefield, originally published in The Lancet, presented supposed evidence that the MMR Vaccine (an immunization against measles, mumps and rubella that is typically first administered to children shortly after their first birthday) was linked to the onset of autism spectrum disorders.[36] The article was widely critisied for lack of scientific rigour and then partially retracted in 2004 by Wakefield's co-authors,[37] and was fully retracted by The Lancet in 2010.[38]

Side effects and injury[edit]

The Centers for Disease Control and Prevention (CDC) has compiled a list of vaccines and their possible side effects.[39] Allegations of vaccine injuries in recent decades have appeared in litigation in the U.S. Some families have won substantial awards from sympathetic juries, even though most public health officials have said that the claims of injuries were unfounded.[40] In response, several vaccine makers stopped production, which the US government believed could be a threat to public health, so laws were passed to shield makers from liabilities stemming from vaccine injury claims.[40]

Routes of administration[edit]

Air France Vaccinations Centre in the 7th arrondissement of Paris

A vaccine administration may be oral, by injection (intramuscular, intradermal, subcutaneous), by puncture, transdermal or intranasal.[41]

See also[edit]


  4. ^
  5. ^ "Tetanus" (PDF). Retrieved 2014-03-01. 
  6. ^ a b c Lombard M, Pastoret PP, Moulin AM (2007). "A brief history of vaccines and vaccination". Rev. - Off. Int. Epizoot. 26 (1): 29–48. PMID 17633292. 
  8. ^ a b Plett PC (2006). "Plett and other discoverers of cowpox vaccination before Edward Jenner". Sudhoffs Arch (in German) 90 (2): 219–32. PMID 17338405. Retrieved 2008-03-12.  Unknown parameter |DUPLICATE_url= ignored (help)
  13. ^ "Vaccine Overview" (PDF). Smallpox Fact Sheet. Retrieved 2008-01-02. 
  14. ^ Rupprecht CE, Briggs D, Brown CM, et al. (March 2010). "Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices". MMWR Recomm Rep 59 (RR–2): 1–9. PMID 20300058. 
  15. ^ Melinda Wharton. National Vaccine Advisory committee U.S.A. national vaccine plan
  16. ^
  17. ^ ""Doctors and diagnosis" ''The difference between Vaccination and Inoculation''". Retrieved 2014-01-08. 
  18. ^ "Edward Jenner - (1749–1823)". 2008-06-01. Retrieved 2009-07-28.
  19. ^ "History - Edward Jenner (1749 - 1823)". BBC. Retrieved 2014-03-01. 
  20. ^ "Edward Jenner - Smallpox and the Discovery of Vaccination"
  21. ^ Diseases of Poultry, 11th ed. Y. M. Saif et al., editors. Iowa State University Press, Ames, IA, 2003.
  22. ^ Lund, Ole; Nielsen, Morten Strunge and Lundegaard, Claus (2005). Immunological Bioinformatics. MIT Press. ISBN 0-262-12280-4
  23. ^ Chaumeton, F.P.; F.V. Me`rat de Vaumartoise. Dictionaire des sciences sciences médicales. Paris: C.L.F. Panckoucke, 1812-1822, lvi (1821).
  24. ^ Curtin, Phillip (1998). "Disease and Empire: The Health of European Troops in the Conquest of Africa". Cambridge University Press. ISBN 0-521-59835-4
  25. ^ Anthony Henricy (ed.) (1796). Lady Mary Wortley Montagu, Letters of the Right Honourable Lady Mary Wortley Montagu:Written During her Travels in Europe, Asia and Africa 1 (4). pp. 167–169. 
  26. ^ Wolfe, Robert M; Sharp, Lisa K (24 August 2002). "Anti-vaccinationists past and present". British Medical Journal (London) 325 (7361): 325. doi:10.1136/bmj.325.7361.430. PMC 1123944. PMID 12193361. 
  29. ^ Salmon DA, Teret SP, MacIntyre CR, Salisbury D, Burgess MA, Halsey NA (2006). "Compulsory vaccination and conscientious or philosophical exemptions: past, present, and future". Lancet 367 (9508): 436–42. doi:10.1016/S0140-6736(06)68144-0. PMID 16458770. 
  30. ^ The fallacy of coverage: uncovering disparities to improve immunization rates through evidence. Results from the Canadian International Immunization Initiative Phase 2 - Operational Research Grants. Sharmila L Mhatre and Anne-Marie Schryer-Roy. BMC International Health and Human Rights 2009, 9(Suppl 1):S1. doi:10.1186/1472-698X-9-S1-S1
  31. ^ "Time to think about vaccinations again", Medicines Talk, Sydney, 3 February 2010.
  32. ^ Public Health Law Research
  33. ^ "Laws and Policies Requiring Specified Vaccinations among High Risk Populations". Retrieved 2014-01-08. 
  34. ^ "Vaccination Requirements for Child Care, School and College Attendance". Retrieved 2014-01-08. 
  35. ^ "Standing Orders for Vaccination". Retrieved 2014-01-08. 
  38. ^ The Editors Of The Lancet (February 2010). "Retraction—Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children". Lancet 375 (9713): 445. doi:10.1016/S0140-6736(10)60175-4. PMID 20137807. Lay summaryBBC News (2010-02-02). 
  39. ^ "Possible Side-effects from Vaccines". 
  41. ^ Plotkin, Stanley A. (2006). Mass Vaccination: Global Aspects - Progress and Obstacles (Current Topics in Microbiology & Immunology). Springer-Verlag Berlin and Heidelberg GmbH & Co. K. ISBN 978-3-540-29382-8. 

Further reading[edit]

  • Largent, Mark A. (2012). Vaccine: The Debate in Modern America. Baltimore: Johns Hopkins University Press. ISBN 978-1-4214-0607-7. 

External links[edit]