Vaccine 32653 226031494 2008-07-16T14:56:44Z McSly 2576398 [[WP:UNDO|Undid]] revision 226031073 by [[Special:Contributions/Jd350503|Jd350503]] ([[User talk:Jd350503|talk]]) rv unsourced assertion {{otheruses}} A '''vaccine''' is a preparation which is used to improve immunity to a particular disease. The term derives from [[Edward Jenner]]'s use of [[cowpox]] ("vacca" means cow in [[Latin]]), which, when administered to [[human]]s, provided them protection against [[smallpox]], the work which [[Louis Pasteur]] and others carried on. Vaccines are based on the concept of [[variolation]] originating in China, in which a person is deliberately infected with a weak form of smallpox. Jenner realized that milkmaids who had contact with cowpox did not get smallpox. The process of distributing and administrating vaccines is referred to as [[vaccination]]. Since vaccination was much safer, smallpox inoculation fell into disuse and was eventually banned in England in 1849. Vaccines can be [[prophylaxis|prophylactic]] (e.g. to prevent or ameliorate the effects of a future [[infection]] by any natural or "wild" [[pathogen]]), or [[Drug therapy|therapeutic]] (e.g. vaccines against cancer are also being investigated; see [[cancer vaccine]]). ==Types== [[Image:ReverseGeneticsFlu.jpg|thumbnail|300px|[[Avian Flu]] vaccine development by [[reverse genetics]] techniques.]] Vaccines may be dead or inactivated organisms or purified products derived from them. There are four types of traditional vaccines[http://www.drspock.com/article/0,1510,4866,00.html]: * Vaccines containing killed microorganisms - these are previously virulent micro-organisms which have been killed with chemicals or heat. Examples are vaccines against [[Influenza vaccine|flu]], [[cholera]], [[bubonic plague]], and [[hepatitis A]]. * Vaccines containing live, [[attenuated virus]] microorganisms - these are live micro-organisms that have been cultivated under conditions that disable their virulent properties or which use closely-related but less dangerous organisms to produce a broad immune response. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include [[yellow fever]], [[measles]], [[rubella]], and [[mumps]]. The live [[tuberculosis]] vaccine is not the [[contagious]] strain, but a related strain called "[[Bacillus Calmette-Guérin|BCG]]"; it is used in the United States very infrequently. * [[Toxoid]]s - these are inactivated toxic compounds in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include [[tetanus]] and [[diphtheria]]. Not all toxoids are for micro-organisms; for example, Crotalis atrox toxoid is used to vaccinate dogs against rattlesnake bites. * [[Subunit]] - rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a fragment of it can create an immune response. Characteristic examples include the subunit vaccine against [[HBV]] that is composed of only the surface proteins of the virus (produced in [[yeast]]) and the [[virus-like particle]] (VLP) vaccine against [[human papillomavirus]] (HPV) that is composed of the viral major [[capsid]] protein. A number of innovative vaccines are also in development and in use: * [[Conjugate vaccine|Conjugate]] - certain bacteria have [[polysaccharide]] outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the [[immune system]] can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the ''Haemophilus influenzae'' type B vaccine. * [[Recombinant DNA|Recombinant]] Vector - by combining the physiology of one micro-organism and the [[DNA]] of the other, immunity can be created against diseases that have complex infection processes * [[DNA vaccination]] - in recent years a new type of vaccine, created from an infectious agent's DNA called ''DNA vaccination'', has been developed. It works by insertion (and [[Gene expression|expression]], triggering immune system recognition) into human or animal cells, of viral or bacterial DNA. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is still experimental. Note that while most vaccines are created using inactivated or attenuated compounds from micro-organisms, [[synthetic vaccine]]s are composed mainly or wholly of synthetic peptides, carbohydrates or antigens. ==Developing immunity== The immune system recognizes vaccine agents as foreign, destroys them, and 'remembers' them. When the [[virulent]] version of an agent comes along the body recognises the protein coat on the virus, and thus is prepared to respond, by (1) neutralizing the target agent before it can enter cells, and (2) by recognizing and destroying infected cells before that agent can multiply to vast numbers. Vaccines have contributed to the eradication of [[smallpox]], one of the most contagious and deadly diseases known to man. Other diseases such as [[rubella]], [[polio]], [[measles]], [[mumps]], [[chickenpox]], and [[typhoid]] are nowhere near as common as they were just a hundred years ago. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called [[herd immunity]]. Polio, which is transmitted only between humans, is targeted by an extensive [[Polio eradication|eradication campaign]] that has seen endemic polio restricted to only parts of four countries.[http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5627a3.htm?s_cid=mm5627a3_e] The difficulty of reaching all children as well as cultural misunderstandings, however, have caused the eradication date to be missed several times. ==Schedule== {{main|Vaccination schedule}} :''See also: [[Vaccination policy]]'' In order to provide best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional 'booster' shots often required to achieve 'full immunity'. This has led to the development of complex vaccination schedules. In the United States, the [[Advisory Committee on Immunization Practices]], which recommends schedule additions for the [[Center for Disease Control]], recommends routine vaccination of children against: [[hepatitis A]], [[hepatitis B]], [[polio]], [[mumps]], [[measles]], [[rubella]], [[diphtheria]], [[pertussis]], [[tetanus]], [[Haemophilus influenzae|HiB]], [[chicken pox]], [[rotavirus]], [[influenza]], [[meningococcal disease]] and [[pneumonia]]. The large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. In order to combat declining compliance rates, various notification systems have been instituted and a number of combination injections are now marketed (e.g., [[Prevnar]] and [[ProQuad vaccine]]s), which provide protection against multiple diseases. Besides recommendations for infant vaccinations and boosters, many specific vaccines are recommended at other ages or for repeated injections throughout life -- most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. The [[human papillomavirus]] vaccine is currently recommended in the U.S. and UK for ages 11–25. Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against [[shingles]], a disease caused by the chicken pox virus, which usually affects the elderly. In [[Australia]], a massive increase in vaccination rates was observed when the federal government made certain benefits (such as the universal 'Family Allowance' welfare payments for parents of children) dependent on vaccination. As well, children were not allowed into school unless they were either vaccinated or their parents completed a statutory declaration refusing to immunize them, after discussion with a doctor, and other bureaucracy. (Similar school-entry vaccination regulations have been in place in some parts of [[Canada]] for several years.) It became easier and cheaper to vaccinate one's children than not to. When faced with the annoyance, many more casual objectors simply gave in.{{Fact|date=January 2008}} ==Efficacy==<!-- This section is linked from [[Mumps]] --> Vaccines do not guarantee complete protection from a disease. Sometimes this is because the host's immune system simply doesn't respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or because the host's immune system does not have a B-cell capable of generating antibodies to that antigen. Even if the host develops antibodies, the human immune system is not perfect and in any case the immune system might still not be able to defeat the infection. [[Immunologic adjuvant|Adjuvant]]s are typically used to boost immune response. Adjuvants are sometimes called the ''dirty little secret'' of vaccines [http://www.thescientist.com/article/display/39377/] in the scientific community, as not much is known about how adjuvants work. Most often aluminium adjuvants are used, but adjuvants like [[squalene]] are also used in some vaccines and more vaccines with squalene and phosphate adjuvants are being tested. The [[vaccine efficacy|efficacy]] or performance of the vaccine is dependent on a number of factors: * the disease itself (for some diseases vaccination performs better than for other diseases) * the strain of vaccine (some vaccinations are for different strains of the disease) [http://bmj.bmjjournals.com/cgi/content/full/319/7206/352] * whether one kept to the timetable for the vaccinations (''see [[Vaccination schedule]]'') * some individuals are 'non-responders' to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly * other factors such as ethnicity or genetic predisposition When a vaccinated individual does develop the disease vaccinated against, the disease is likely to be milder than without vaccination. The following are important considerations in the effectiveness of a vaccination program:{{Fact|date=January 2008}} # careful modelling to anticipate the impact that an immunisation campaign will have on the epidemiology of the disease in the medium to long term # ongoing surveillance for the relevant disease following introduction of a new vaccine and # maintaining high immunisation rates, even when a disease has become rare. ==Types of vaccine developments== {{Unreferencedsect|date=June 2008}} * ''Rational attenuation'' Specific modifications or deletions of genes that confer virulence removes the pathogenicity of the microbe while still allowing an immune response to be generated. This type of rational attenuation can be viewed as creating a "live" attenuated vaccine. * ''Vector-mediated subunit delivery'' Introducing a non-infectious, non-pathogenic subunit into a live vector can prompt an immune response without presence of the pathogen. This is called ''vector-mediated subunit delivery''. For example, rabies surface protein gene has been inserted into vaccinia virus. * ''[[Virus-like particle]]s'' Capsid proteins of icosahedral viruses assemble without the presence of a genome. These virus-like particles are antigenically authentic, but non-infectious. This has been used for HPV-16 and HPV-18 vaccines. ==Controversy== [[Image:The cow pock.jpg|thumb|[[James Gillray]], ''The Cow-Pock—or—the Wonderful Effects of the New Inoculation!'' (1802)]] {{main|Vaccine controversy}} [[Antivaccinationist|Opposition to vaccination]], from a wide array of vaccine critics, has existed since the earliest vaccination campaigns.<ref name=wolfesharp>{{cite journal |author= Wolfe R, Sharp L |title= Anti-vaccinationists past and present |journal=BMJ |volume=325 |issue=7361 |pages=430–2 |year=2002 |pmid=12193361 |doi=10.1136/bmj.325.7361.430 |url=http://bmj.bmjjournals.com/cgi/content/full/325/7361/430}}</ref> Disputes have arisen over the morality, ethics, effectiveness, and safety of vaccination. The mainstream medical opinion is that the benefits of preventing suffering and death from serious [[infectious disease]]s greatly outweigh the risks of rare [[adverse effect]]s following [[immunization]].<ref name=BH>{{cite journal |journal= Curr Opin Infect Dis |year=2007 |volume=20 |issue=3 |pages=237–46 |title= Adverse events following immunization: perception and evidence |author= Bonhoeffer J, Heininger U |doi=10.1097/QCO.0b013e32811ebfb0 |pmid=17471032}}</ref><ref name=Cochrane>{{cite journal |doi=10.1002/14651858.CD004407.pub2 |pmid=16235361 |title= Vaccines for measles, mumps and rubella in children |author=Demicheli V, Jefferson T, Rivetti A, Price D |journal= Cochrane Database Syst Rev |year=2005 |volume=19 |issue=4 |laysummary=http://www.cochrane.org/press/MMR_final.pdf |laydate=2005-10-19 |laysource=Cochrane press release (PDF)}}</ref> Some vaccination critics say that vaccines are ineffective against disease<ref name=Halvorsen>{{cite book |author= Halvorsen R |title= The Truth about Vaccines |publisher= Gibson Square |date=2007 |isbn=9781903933923}}</ref> or that vaccine safety studies are inadequate.<ref name=Cochrane/><ref name=Halvorsen/> Some religious groups oppose vaccination as a matter of [[doctrine]],<ref name=White>{{cite book |chapter= Theological opposition to inoculation, vaccination, and the use of anæsthetics |title= A History of the Warfare of Science with Theology in Christendom |author= White AD |location= New York |publisher=Appleton |year=1896 |chapterurl=http://abob.libs.uga.edu/bobk/whitem10.html |accessdate=2007-08-17}}</ref> and some political groups oppose mandatory vaccination on the grounds of [[Liberty|individual liberty]].<ref name=wolfesharp/> ==Economics of development== One challenge in vaccine development is economic: many of the diseases most demanding a vaccine, including [[HIV]], [[malaria]] and [[tuberculosis]], exist principally in poor countries. Pharmaceutical firms and biotech companies have little incentive to develop vaccines for these diseases, because there is little revenue potential. Even in more affluent countries, financial returns for producing vaccines are usually minimal, and the risks are great.<ref name='market_return'>{{cite news | first=Jesse L. | last=Goodman | coauthors= | title=Statement of Jesse L. Goodman, M.D., M.P.H. Director, Center for Biologics, Evaluation and Research Before the Committee on Energy and Commerce United States House of Representatives | date=2005-05-04 | publisher= | url =http://www.fda.gov/ola/2005/influenza0504.html | work = | pages = | accessdate = 2008-06-15 | language = }}</ref> Most vaccine development to date has relied on 'push' funding by government, universities and non-profit organizations.{{Fact|date=June 2008}} Many vaccines have been highly cost effective and beneficial for public health.<ref name='market_return' /> The number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools may be due to government mandates and support, rather than economic incentive.{{Fact|date=June 2008}} Many researchers and policymakers are calling for a different approach, using 'pull' mechanisms to motivate industry. Mechanisms such as prizes, tax credits, or [[advance market commitments]] could ensure a financial return to firms that successfully developed a HIV vaccine. If the policy were well-designed, it might also ensure people have access to a vaccine if and when it is developed.{{Fact|date=June 2008}} ==Intellectual property== [[Intellectual property]] can also be viewed as an obstacle to the development of new vaccines. Because of the weak protection offered through the [[patent]] of the final product, the protection of the innovation regarding vaccines is often made through the [[patent]] of processes used on the development of new vaccines as well as the protection of [[secrecy]].<ref>{{cite journal |author= Hardman Reis T |title= The role of intellectual property in the global challenge for immunization |journal= J World Intellect Prop |date=2006 |volume=9 |issue=4 |pages=413–25 |doi=10.1111/j.1422-2213.2006.00284.x}}</ref> ==Preservatives== Many vaccines need preservatives to prevent serious adverse effects such as the ''[[Staphylococcus]]'' infection that in one 1928 incident killed 12 of 21 children inoculated with a [[diphtheria]] vaccine that lacked a preservative.<ref>{{cite web |date=2007-09-06 |url=http://www.fda.gov/cber/vaccine/thimerosal.htm |accessdate=2007-10-01 |title= Thimerosal in vaccines |publisher= Center for Biologics Evaluation and Research, U.S. Food and Drug Administration}}</ref> Several preservatives are available, including [[thiomersal]], [[2-phenoxyethanol]], and [[formaldehyde]]. Thiomersal is more effective against bacteria, has better shelf life, and improves vaccine stability, potency, and safety, but in the U.S., the [[European Union]], and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its [[Mercury (element)|mercury]] content.<ref>{{cite journal |journal= Drug Saf |date=2005 |volume=28 |issue=2 |pages=89–101 |title= Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease |author= Bigham M, Copes R |pmid=15691220}}</ref> [[Thiomersal controversy|Controversial claims]] have been made that thiomersal contributes to [[autism]]; no convincing scientific evidence supports these claims.<ref>{{cite journal |journal= N Engl J Med |year=2007 |volume=357 |issue=13 |pages=1278–9 |title= Thimerosal and vaccines—a cautionary tale |author= [[Paul Offit|Offit PA]] |doi=10.1056/NEJMp078187 |pmid=17898096 |url=http://content.nejm.org/cgi/content/full/357/13/1278}}</ref> ==Delivery systems== There are several new delivery systems in development, which will hopefully make vaccines more efficient to deliver. Possible methods include [[liposome]]s and ''ISCOM''<ref>[http://www.cababstractsplus.org/google/abstract.asp?AcNo=20043185919 Advanced Drug Delivery Reviews, 2004 (Vol. 56) (No. 10) 1367-1382] Morein, B., Hu KeFei, Abusugra, I</ref> (immune stimulating complex). ===Plasmids=== The use of [[plasmid]]s has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, the crossover application into human studies has been met with poor results based on the inability to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's immunogenicity while also correcting for factors involved in the specific activation of immune effector cells. <ref name= Lowe>{{cite book |chapterurl=http://www.horizonpress.com/pla|author= Lowe et al|year=2008|chapter=Plasmid DNA as Prophylactic and Therapeutic vaccines for Cancer and Infectious Diseases|title=Plasmids: Current Research and Future Trends|publisher=Caister Academic Press|id=[http://www.horizonpress.com/pla ISBN 978-1-904455-35-6]}}</ref> ==Use in nonhumans== {{Seealso|Influenza vaccine#Flu vaccine for nonhumans|Vaccination of dogs}} Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans. Both animals kept as pets and animals raised as stock are vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control [[rabies]] in [[raccoon]]s. Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include [[canine distemper]], [[canine parvovirus]], [[canine hepatitis virus]], [[adenovirus-2]], [[leptospirosis]], [[bordatella]], [[canine parainfluenza virus]], and [[Lyme disease]] among others. ==See also== <div style="-moz-column-count:3; column-count:3;"> * [[Influenza vaccine]] * [[Immune system]] * [[OPV AIDS hypothesis]], a refuted hypothesis that the AIDS pandemic emerged from polio vaccine manufacture. * [[Immunology]] * [[Immunization]] * [[Inoculation]] * [[TA-CD]], a vaccine which negates the effects of [[cocaine]] * [[The Horse Named Jim]] * [[Virosomes]] * [[Vaccination]] * [[List of vaccine topics]] </div> ==References== {{reflist|2}} ==External links== * {{dmoz|Health/Pharmacy/Drugs_and_Medications/Vaccines_and_Antisera|Vaccines and Antisera}} * {{cite web |title=Immunization |url=http://www.nlm.nih.gov/medlineplus/immunization.html |date=2007-12-27 |accessdate=2008-01-14 |work=MedlinePlus |publisher= U.S. National Library of Medicine}} * [http://www.violinet.org/ VIOLIN]: Vaccine Investigation and Online Information Network {{Vaccines}} {{Major Drug Groups}} [[Category:Virology]] [[Category:Vaccination]] [[Category:Infectious diseases]] [[Category:Microbiology]] [[Category:Immunology]] {{Link FA|vi}} [[ar:تطعيم]] [[gn:Tasymombiaha]] [[ca:Vacuna]] [[cs:Vakcína]] [[da:Vaccination]] [[de:Impfstoff]] [[es:Vacuna]] [[eo:Vakcino]] [[fa:واکسن]] [[fr:Vaccination]] [[fur:Vacine]] [[ko:백신]] [[id:Vaksin]] [[it:Vaccino]] [[he:חיסון]] [[nl:Vaccin]] [[ja:ワクチン]] [[no:Vaksine]] [[nn:Vaksine]] [[pl:Szczepionka]] [[pt:Vacina]] [[ro:Vaccin]] [[ru:Вакцина]] [[sk:Očkovanie]] [[sl:Cepivo]] [[fi:Rokotus]] [[te:టీకా]] [[th:วัคซีน]] [[vi:Vắc-xin]] [[uk:Вакцина]] [[zh:疫苗]]