Difference between revisions of "Vaccine"

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[[Image:SalkatPitt.jpg|thumb|180px|[[Jonas Salk]] in 1955 holds two bottles of a culture used to grow [[polio]] vaccines.]]
 
 
A '''vaccine''' is a biological preparation that improves immunity to a particular [[disease]]. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's [[immune system]] to recognize the agent as foreign, destroy it, and keep a record of it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.
 
A '''vaccine''' is a biological preparation that improves immunity to a particular [[disease]]. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's [[immune system]] to recognize the agent as foreign, destroy it, and keep a record of it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.
  
 
Vaccines can be [[prophylaxis|prophylactic]] (example: to prevent or ameliorate the effects of a future [[infection]] by any natural or "wild" [[pathogen]]), or [[Medication|therapeutic]] (e.g., vaccines against cancer are also being investigated; see [[cancer vaccine]]).
 
Vaccines can be [[prophylaxis|prophylactic]] (example: to prevent or ameliorate the effects of a future [[infection]] by any natural or "wild" [[pathogen]]), or [[Medication|therapeutic]] (e.g., vaccines against cancer are also being investigated; see [[cancer vaccine]]).
  
The terms'' vaccine'' and ''vaccination'' are derived from ''Variolae vaccinae'' (smallpox of the cow), the term devised by [[Edward Jenner]] to denote [[cowpox]]. He used it in 1798 in the long title of his ''Inquiry into the...Variolae vaccinae...known...[as]...the Cow Pox'', in which he described the protective effect of cowpox against [[smallpox]].<ref name=Baxby1999>{{cite journal|last=Baxby|first=Derrick|title=Edward Jenner's Inquiry; a bicentenary analysis|journal=Vaccine|year=1999|volume=17|issue=4|pages=301–7}}</ref> In 1881, to honour Jenner, [[Louis Pasteur]] proposed that the terms  should be extended to cover the new protective inoculations then being developed.<ref name=Pasteur1881>{{cite journal|last=Pasteur|first=Louis|title=Address on the Germ Theory|journal=Lancet|year=1881|volume=118|issue=3024|pages=271–2}}</ref>
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The terms'' vaccine'' and ''vaccination'' are derived from ''Variolae vaccinae'' (smallpox of the cow), the term devised by [[Edward Jenner]] to denote [[cowpox]]. He used it in 1798 in the long title of his ''Inquiry into the...Variolae vaccinae...known...[as]...the Cow Pox'', in which he described the protective effect of cowpox against [[smallpox]].
 
 
==Effectiveness==<!-- This section is linked from [[Mumps]] -->
 
Vaccines do not guarantee complete protection from a disease.<ref>{{cite journal | last1 = Grammatikos | first1 = Alexandros P. | last2 = Mantadakis | first2 = Elpis | last3 = Falagas | first3 = Matthew E. | title = Meta-analyses on Pediatric Infections and Vaccines | url = |pmid = 19393917 | journal = Infectious Disease Clinics of North America | doi=10.1016/j.idc.2009.01.008 | volume=23 | issue=2 |date=June 2009 | pages=431–57}}</ref> Sometimes, this is because the host's immune system simply does not respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection, age) or because the host's immune system does not have a [[B cell]] capable of generating [[Antibody|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 immediately. In this case, the infection will be less severe and heal faster.
 
 
 
[[Immunologic adjuvant|Adjuvants]] are typically used to boost immune response. 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. Larger doses are used in some cases for older people (50–75 years and up), whose immune response to a given vaccine is not as strong.<ref name=neighmond2010>{{cite news | url=http://www.npr.org/templates/story/story.php?storyId=123406640 | title=Adapting Vaccines For Our Aging Immune Systems | date=2010-02-07 | work=Morning Edition | publisher=NPR | accessdate=2014-01-09 | last=Neighmond | first=Patti | deadurl=no | archiveurl=http://archive.is/z9wC | archivedate=2012-09-05 }}{{open access}}</ref>
 
[[File:Hilleman-Walter-Reed.jpeg|thumb|120px|[[Maurice Hilleman]]'s measles vaccine is estimated to prevent 1 million deaths every year.<ref name=sullivan2005>{{cite news | last=Sullivan | first=Patricia | date=2005-04-13 | url=http://www.washingtonpost.com/wp-dyn/articles/A48244-2005Apr12.html | title=Maurice R. Hilleman dies; created vaccines | work=Wash. Post | accessdate=2014-01-09 | deadurl=no | archiveurl=http://archive.is/UyNX | archivedate=2012-09-15 }}{{open access}}</ref>]]
 
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)<ref>{{cite journal | url=http://www.bmj.com/content/319/7206/352 | doi=10.1136/bmj.319.7206.352 | pmid=10435956 | title=Comparative efficacy of three mumps vaccines during disease outbreak in eastern Switzerland: cohort study | last=Schlegel ''et al.'' | volume=319 | issue=7206 | page=352 | journal=BMJ  | date=August 1999 | accessdate=2014-01-09 }}{{open access}}</ref>
 
* 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, age, or genetic predisposition.
 
 
 
When a vaccinated individual does develop the disease vaccinated against, the disease is likely to be milder than without vaccination.<ref>{{cite journal|last1=Préziosi|first1=M.|last2=Halloran|first2=M.E.|year=2003|title=Effects of Pertussis Vaccination on Disease: Vaccine Efficacy in Reducing Clinical Severity|journal=Clinical Infectious Diseases|volume=37|issue=6|pages=772–779|publisher=Oxford Journals|doi=10.1086/377270| url=http://cid.oxfordjournals.org/content/37/6/772.full}}</ref>
 
 
 
The following are important considerations in the effectiveness of a vaccination program:{{Citation needed|date=January 2008}}
 
# careful modelling to anticipate the impact that an immunization 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
 
# maintaining high immunization rates, even when a disease has become rare.
 
 
 
In 1958, there were 763,094 cases of measles and 552 deaths in the [[United States]].<ref name="pmid15106120">{{cite journal |author=Orenstein WA, Papania MJ, Wharton ME |title=Measles elimination in the United States |journal=J Infect Dis |volume=189 |issue=Suppl 1 |pages=S1–3|year=2004 |pmid=15106120 |doi=10.1086/377693 |url=http://www.journals.uchicago.edu/doi/full/10.1086/377693 }}</ref><ref name="pmid18463608">{{cite journal | author=<!--staff--> | title=Measles—United States, January 1 – April 25, 2008 | journal=Morb. Mortal. Wkly. Rep. | volume=57 | issue=18 | pages=494–8 |date=May 2008 | pmid=18463608 | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5718a5.htm }}{{open access}}</ref> With the help of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).<ref name="pmid18463608"/> In early 2008, there were 64 suspected cases of measles. Fifty-four out of 64 infections were associated with importation from another country, although only 13% were actually acquired outside of the United States; 63 of these 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated.<ref name="pmid18463608"/>
 
==Adverse effects==
 
Adverse effects if any are generally mild.<ref name=CDC2013>{{cite web|title=Possible Side-effects from Vaccines|url=http://www.cdc.gov/vaccines/vac-gen/side-effects.htm|work=Centers for Disease Control and Prevention|accessdate=24 February 2014}}</ref> The rate of side effects depends on the vaccine in question.<ref name=CDC2013/> Some potential side effects include: fever, pain around the injection site, and muscle aches.<ref name=CDC2013/>
 
 
 
==Types==
 
[[File:ReverseGeneticsFlu.svg|thumbnail|300px|[[Avian influenza|Avian flu]] vaccine development by [[reverse genetics]] techniques.]]
 
Vaccines are dead or inactivated organisms or purified products derived from them.
 
 
 
There are several types of vaccines in use.<ref>{{cite web|url=http://www.niaid.nih.gov/topics/vaccines/understanding/pages/typesvaccines.aspx |title=Vaccine Types |publisher=Niaid.nih.gov |date=2012-04-03 |accessdate=2013-04-26}}</ref> These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response.
 
 
 
===Killed===
 
Some vaccines contain killed, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, radioactivity, or antibiotics. Examples are the [[influenza vaccine]], [[cholera vaccine]], [[bubonic plague vaccine]], [[polio vaccine]], [[hepatitis A vaccine]], and [[rabies vaccine]].
 
 
 
===Attenuated===
 
Some vaccines contain live, [[attenuated vaccine|attenuated]] microorganisms. Many of these are active [[viruses]] that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases [[yellow fever]], [[measles]], [[rubella]], and [[mumps]], and the bacterial disease [[typhoid]]. The live Mycobacterium [[tuberculosis]] vaccine developed by Calmette and Guérin is not made of a [[Infectious disease|contagious]] strain, but contains a virulently modified strain called "[[Bacillus Calmette-Guérin|BCG]]" used to elicit an immune response to the vaccine. The live attenuated vaccine-containing strain [[Yersinia pestis]] EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. They typically provoke more durable immunological responses and are the preferred type for healthy adults. But they may not be safe for use in immunocompromised individuals, and may rarely mutate to a virulent form and cause disease.<ref name="Bhattacharya">{{cite book | author=J.K. Sinha & S. Bhattacharya | title=A Text Book of Immunology | url=http://books.google.com/books?id=ytCNCbCWx8oC&pg=PA318 | format=Google Book Preview | accessdate=2012-03-16 | publisher=Academic Publishers | isbn=978-81-89781-09-5 | page=318 | accessdate=2014-01-09 }}</ref>
 
 
 
===Toxoid===
 
{{Main|Toxoid}}
 
[[Toxoid]] vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include [[tetanus]] and [[diphtheria]]. Toxoid vaccines are known for their efficacy. Not all toxoids are for micro-organisms; for example, ''[[Crotalus atrox]]'' toxoid is used to vaccinate dogs against [[rattlesnake]] bites.
 
===Subunit===
 
[[Protein subunit]]&nbsp;– 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. Examples include the subunit vaccine against [[Hepatitis B virus]] that is composed of only the surface proteins of the virus (previously extracted from the [[blood serum]] of chronically infected patients, but now produced by [[recombinant DNA|recombination]] of the viral genes into [[yeast]]), the [[virus-like particle]] (VLP) vaccine against [[human papillomavirus]] (HPV) that is composed of the viral major [[capsid]] protein, and the [[hemagglutinin]] and [[neuraminidase]] subunits of the [[influenza]] virus. Subunit vaccine is being used for plague immunization.
 
 
 
===Conjugate===
 
[[Conjugate vaccine|Conjugate]]&nbsp;– 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.
 
 
 
===Experimental===
 
[[File:Agile Pulse In Vivo.jpg|57 KBpx|thumbnail|default|Agile Pulse In Vivo Electroporation System for enhanced vaccine delivery manufactured by BTX Harvard Apparatus, Holliston MA USA]]
 
A number of innovative vaccines are also in development and in use:
 
* Dendritic cell vaccines combine [[dendritic cell]]s with antigens in order to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors.<ref>{{cite journal |author=Kim W, Liau LM |title=Dendritic cell vaccines for brain tumors |journal=Neurosurg Clin N Am |volume=21 |issue=1 |pages=139–57 |year=2010 |pmid=19944973 |pmc=2810429 |doi=10.1016/j.nec.2009.09.005 }}</ref>
 
* [[Recombinant DNA|Recombinant]] Vector&nbsp;– 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]]&nbsp;– in recent years{{When|date=July 2011}} a new type of vaccine called ''DNA vaccination'', created from an infectious agent's DNA, has been developed. It works by insertion (and [[Gene expression|expression]], enhanced by the use of [[electroporation]], triggering immune system recognition) of viral or bacterial DNA into human or animal cells. 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.
 
* [[T-cell receptor]] peptide vaccines are under development for several diseases using models of [[Valley Fever]], [[stomatitis]], and [[atopic dermatitis]]. These peptides have been shown to modulate [[cytokine]] production and improve cell mediated immunity.
 
* Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.<ref>{{cite journal | pmid = 19388175 | last1 = Meri | first1 = S | last2 = Jördens | first2 = M | last3 = Jarva | first3 = H | title = Microbial complement inhibitors as vaccines | journal = Vaccine | volume=26 Suppl 8 |date=December 2008 | pages=I113–7 | doi = 10.1016/j.vaccine.2008.11.058}}</ref>
 
 
 
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.
 
 
 
===Valence===
 
Vaccines may be ''monovalent'' (also called ''univalent'') or ''multivalent'' (also called ''polyvalent''). A monovalent vaccine is designed to immunize against a single antigen or single microorganism.<ref>{{DorlandsDict|five/000067458.htm|Monovalent}}</ref> A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.<ref>[http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSz000113928zPzhtm Polyvalent vaccine]{{dead link|date=January 2014}} at ''[[Dorland's medical reference works|Dorlands Medical Dictionary]]''</ref> The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., ''tetravalent'' or ''quadrivalent'').  In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.<ref>{{cite web|url=http://www.pediatriconcall.com/fordoctor/medical_original_articles/oral_polio_vaccine.asp|title=Questions and answers on monovalent oral polio vaccine type 1 (mOPV1) "Issued jointly by WHO and UNICEF"}}</ref>
 
 
 
===Heterotypic===
 
Also known as [[heterologous vaccine|Heterologous]] or "Jennerian" vaccines these are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of [[BCG]] vaccine made from [[Mycobacterium bovis]] to protect against human tuberculosis.<ref>{{cite journal|last=Scott|title=Classifying Vaccines|journal=BioProcesses International|date=April 2004|pages=14–23|url=http://www.bioprocessintl.com/multimedia/archive/00077/0204su03_77445a.pdf|accessdate=2014-01-09}}</ref>
 
 
 
==Developing immunity==
 
The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the [[virulence|virulent]] version of an agent is encountered, the body recognizes 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) recognizing and destroying infected cells before that agent can multiply to vast numbers.
 
 
 
When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first noted in the trivalent Sabin [[polio vaccine]], where the amount of serotype 2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype 1 and 3 viruses in the vaccine.<ref>{{cite book|author=Sutter RW, Cochi SL, Melnick JL|year=1999|chapter=Live attenuated polio vaccines|editor=Plotkin SA, Orenstein WA (eds.)|title=Vaccines|location=Philadelphia|publisher=W. B. Saunders|pages=364–408}}</ref> This phenomenon has also been found to be a problem with the [[dengue]] vaccines currently being researched,{{When|date=July 2011}} where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, −2 and −4 serotypes.<ref>{{cite journal|author=Kanesa-thasan N|year=2001|title=Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers|journal=Vaccine|volume=19|issue=23–24|pages=3179–3188|pmid=11312014|doi=10.1016/S0264-410X(01)00020-2|author-separator=,|author2=Sun W|author3=Kim-Ahn G|display-authors=3|last4=Van Albert|first4=S.|last5=Putnak|first5=J.R.|last6=King|first6=A.|last7=Raengsakulsrach|first7=B.|last8=Christ-Schmidt|first8=H.|last9=Gilson|first9=K.}}</ref>
 
 
 
Vaccines have contributed to the eradication of [[smallpox]], one of the most contagious and deadly diseases known to man. Other diseases such as rubella, [[poliomyelitis|polio]], measles, mumps, [[chickenpox]], and [[typhoid fever|typhoid]] are nowhere near as common as they were 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 [[Poliomyelitis eradication|eradication campaign]] that has seen endemic polio restricted to only parts of four countries ([[Afghanistan]], [[India]], [[Nigeria]], and [[Pakistan]]).<ref name=mmwr5627>{{cite journal | url=http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5627a3.htm | title=Progress Toward Interruption of Wild Poliovirus Transmission—Worldwide, January 2006 – May 2007 | journal=Morb. Mortal. Wkly. Rep. | date=2007-07-13 | accessdate=2013-04-26 | accessdate=2014-01-09 | volume=56 | issue=27 | pages=682–5 | deadurl=no | archiveurl=http://archive.is/Vkjun | archivedate=2014-01-09 }}{{open access}}</ref>  The difficulty of reaching all children as well as cultural misunderstandings, however, have caused the anticipated eradication date to be missed several times.
 
 
 
==Schedule==
 
{{main|Vaccination schedule}}
 
:''For country-specific information on vaccination policies and practices, see: [[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 [[Centers for Disease Control and Prevention]], recommends routine vaccination of children against:<ref>{{cite web | url=http://www.cdc.gov/vaccines/hcp/acip-recs/index.html | title=ACIP Vaccine Recommendations Home Page | author=<!--staff--> | publisher=CDC | accessdate=2014-01-10 | date=2013-11-15<!--last update--> | deadurl=no | archiveurl=http://archive.is/KAYi5 | archivedate=2014-01-10 }}</ref> [[hepatitis A]], [[hepatitis B virus|hepatitis B]], polio, mumps, measles, rubella, [[diphtheria]], [[pertussis]], [[tetanus]], [[Haemophilus influenzae|HiB]], chickenpox, [[rotavirus]], [[influenza]], [[meningococcal disease]] and [[pneumonia]].<ref>{{cite web | url=http://aapredbook.aappublications.org/site/news/vaccstatus.xhtml | title=Vaccine Status Table | work=Red Book Online | publisher=American Academy of Pediatrics | date=April 26, 2011 | accessdate=January 9, 2013 }}</ref> 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., [[Pneumococcal conjugate vaccine]] and [[MMRV vaccine]]), 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 recommended in the U.S. (as of 2011)<ref>{{cite web | title=HPV Vaccine Safety | url=http://www.cdc.gov/vaccinesafety/Vaccines/HPV/Index.html | publisher=Centers for Disease Control and Prevention (CDC) | date=2013-12-20<!--last update--> | accessdate=2014-01-10 | deadurl=no | archiveurl=http://archive.is/minO | archivedate=2014-01-10 }}</ref> and UK (as of 2009).<ref>{{cite news | title=HPV vaccine in the clear | author=<!--staff--> | url=http://www.nhs.uk/news/2009/09September/Pages/Cervical-cancer-vaccine-QA.aspx | work=NHS choices | date=2009-10-02 | accessdate=2014-01-10 | deadurl=no | archiveurl=http://archive.is/yX7A | archivedate=2012-09-07 }}{{open access}}</ref> Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against [[Herpes zoster|shingles]], a disease caused by the chickenpox virus, which usually affects the elderly.
 
 
 
==History==
 
[[File:Eduard Jenner.jpg|thumb|160px|Edward Jenner]]
 
Prior to the introduction of vaccination with material from cases of cowpox (heterotypic immunisation), smallpox could be prevented by deliberate [[inoculation]] of smallpox virus, later referred to as [[variolation]] to distinguish it from [[smallpox vaccine|smallpox vaccination]]. This information was [[Inoculation#Importation to the West|brought to the West]] in 1721 by [[Lady Mary Wortley Montagu]], who showed it to [[Hans Sloane]], the King's physician.<ref>{{cite news | url=http://www.independent.co.uk/news/science/how-islamic-inventors-changed-the-world-469452.html | department=Science | location=London | newspaper=Indep. | title=How Islamic inventors changed the world | author=<!--staff--> | date=2006-03-11 | accessdate=2014-01-10 | deadurl=no | archiveurl=http://archive.is/I6Jo | archivedate=2012-07-16 }}</ref>
 
 
 
Sometime during the late 1760s whilst serving his apprenticeship as a surgeon/apothecary [[Edward Jenner]] learned of the story, common in rural areas, that dairy workers would never have the often-fatal or disfiguring disease [[smallpox]], because they had already had [[cowpox]], which has a very mild effect in humans. In 1796, Jenner took pus from the hand of a milkmaid with cowpox, scratched it into the arm of an 8-year-old boy, and six weeks later inoculated ([[Variolation|variolated]]) the boy with smallpox, afterwards observing that he did not catch smallpox.<ref name=Stern-Markel>{{cite journal | author=Stern AM, Markel H | title=The history of vaccines and immunization: familiar patterns, new challenges | journal=Health Aff. | volume=24 | issue=3 | pages=611–21 | year=2005 | pmid=15886151 | doi=10.1377/hlthaff.24.3.611 | url=http://content.healthaffairs.org/content/24/3/611.full }}{{open access}}</ref><ref name=Dunn>{{cite journal |author=Dunn PM |title=Dr Edward Jenner (1749–1823) of Berkeley, and vaccination against smallpox |journal=Arch. Dis. Child. Fetal Neonatal Ed. |volume=74 |issue=1 |pages=F77–8 |date=January 1996 |pmid=8653442 |pmc=2528332 |doi=10.1136/fn.74.1.F77|url=http://fn.bmjjournals.com/content/74/1/F77.full.pdf}}</ref> Jenner extended his studies and in 1798 reported that his vaccine was safe in children and adults and could be tranferred from arm-to-arm reducing reliance on uncertain supplies from infected cows.<ref name=Baxby1999/> Since vaccination with cowpox was much safer than smallpox inoculation,<ref>{{cite journal |title=The Vaccinators: Smallpox, Medical Knowledge, and the 'Opening' of Japan |author=Van Sant JE |journal=J Hist Med Allied Sci |year=2008|doi=10.1093/jhmas/jrn014 |volume=63 |issue=2 |pages=276–9 }}</ref> the latter, though still widely practised in England, was banned in 1840.<ref>{{cite journal |title=Development of smallpox vaccine in England in the eighteenth and nineteenth centuries |journal=BMJ|issue=5342 |pages=1367–72 |year=1963 |author=Dudgeon JA |doi=10.1136/bmj.1.5342.1367 |volume=<!--Pacify citation bot--> |pmid=20789814|pmc=2124036}}</ref> The second generation of vaccines was introduced in the 1880s by [[Louis Pasteur]] who developed vaccines for chicken cholera and [[anthrax]],<ref name=Pasteur1881/> and from the late nineteenth century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.<ref name="Stern-Markel" />
 
 
 
The twentieth century saw the introduction of several successful vaccines, including those against [[diphtheria]], [[measles]], [[mumps]], and [[rubella]]. Major achievements included the development of the [[polio vaccine]] in the 1950s and the [[eradication of smallpox]] during the 1960s and 1970s. [[Maurice Hilleman]] was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including [[herpes|herpes simplex]], [[malaria]], and [[HIV]].<ref name="Stern-Markel"/>
 
 
 
===Landmarks in history of vaccines===
 
{| class="wikitable collapsible collapsed"
 
|-
 
! Year !! Landmark
 
|-
 
| 1000 || Chinese practicing [[variolation]]
 
|-
 
| 1545 || [[Smallpox]] epidemic in India
 
|-
 
| 1578 || Whooping cough epidemic in Paris
 
|-
 
| 1625 || Early smallpox in North America
 
|-
 
| 1633 || [[Colonial epidemic]] of smallpox in Massachusetts
 
|-
 
| 1661 || [[Kangxi Emperor]] gives royal support for inoculation.
 
|-
 
| 1676 || [[Thomas Sydenham]] documents [[Measles]] infection
 
|-
 
| 1676 || "The Indian Plague" in [[Iroquois]] documented by [[Louis de Buade de Frontenac]]
 
|-
 
| 1694 || [[Mary II of England|Queen Mary II]] dies of smallpox on 28 December.
 
|-
 
| 1699 || Yellow Fever outbreak in the American Colonies.
 
|-
 
| 1718 || [[Lady Mary Wortley Montagu|Lady Mary Montagu]] had her 6-year old son variolated in Constantinople by [[Charles Maitland (physician)|Dr. Charles Maitland]]
 
|-
 
| 1721 || [[Lady Mary Wortley Montagu|Lady Mary Montagu]] had her 2-year old daughter variolated in England by [[Charles Maitland (physician)|Dr. Charles Maitland]]
 
|-
 
| 1736 || [[Benjamin Franklin|Benjamin Franklin’s]] 4-year-old son dies of smallpox.
 
|-
 
| 1740 || [[Friedrich Hoffmann]] gives first description of [[rubella]]
 
|-
 
| 1757 || [[Francis Home]] demonstrates infectious nature of [[measles]]
 
|-
 
| 1798 || [[Edward Jenner]] publishes his account of the effects of his [[smallpox]] vaccine
 
|-
 
| 1800 || [[Benjamin Waterhouse]] brings smallpox vaccination to United States
 
|-
 
| 1817 || [[Cholera]] pandemic begins
 
|-
 
| 1817 || [[Peter Ludvig Panum|Panum]] studies epidemiology of measles in [[Faroe Islands]]
 
|-
 
| 1854 || [[Filippo Pacini]] isolates [[Vibrio cholerae]]
 
|-
 
| 1874 || A compulsory smallpox vaccination and revaccination law goes into effect in Germany<ref>{{cite web|title=German Vaccination Law|url=http://archive.org/details/vaccinationlawa00germgoog|work=Internet Archive|accessdate=29 November 2012}}</ref>
 
|-
 
| 1880 || [[Louis Pasteur]] develops attenuated fowl cholera vaccine
 
|-
 
| 1881 || [[Louis Pasteur]]'s public trial of [[anthrax]] vaccine at Pouilly le Fort
 
|-
 
| 1881 || [[Louis Pasteur]] and [[George Miller Sternberg|George Sternberg]] independently discover [[Pneumococcus]]
 
|-
 
| 1882 || [[Robert Koch|Koch]] isolates [[Mycobacterium tuberculosis]]
 
|-
 
| 1885 || [[Louis Pasteur]] successfully prevents rabies in [[Joseph Meister]] by post-exposure vaccination
 
|-
 
| 1888 || [[Pasteur Institute|Institut Pasteur]] inaugurated on 14 November
 
|-
 
| 1890 || [[Shibasaburo Kitasato]] and [[Emil Adolf von Behring|Emil von Behring]] immunize guinea pigs with heat-treated diphtheria toxin
 
|-
 
| 1892 || [[Richard Friedrich Johannes Pfeiffer|Pfeiffer]] discovers [[Haemophilus influenzae|Pfeiffer influenza bacillus]]
 
|-
 
| 1894 || First major documented polio outbreak in the United States occurs in Rutland County, Vermont
 
|-
 
| 1896 || [[Robert Koch|Koch]] reports discovery of [[Vibrio cholerae|Cholera vibrio]] unaware of [[Filippo Pacini]]'s work
 
|-
 
| 1898 || English [[Vaccination Act]] allows exemption from smallpox vaccination on grounds of conscience
 
|-
 
| 1899 || [[Yellow fever]] epidemics among [[Panama Canal]] workers, resulting in transfer of project rights from France to United States
 
|-
 
| 1900 || [[Walter Reed]] discovers that yellow fever is transmitted by mosquitoes after studying it in [[Cuba]]
 
|-
 
| 1906 || [[Jules Bordet]] and [[Octave Gengou]] isolate [[Bordetella pertussis]]
 
|-
 
| 1908 || [[Karl Landsteiner]] and [[Erwin Popper]] discover poliovirus
 
|-
 
| 1924 || [[Bacille Calmette-Guerin|BCG]] is introduced as live [[tuberculosis]] vaccine
 
|-
 
| 1935 || [[Max Theiler]] develops live attenuated 17D yellow fever vaccine
 
|-
 
| 1945 || Chick embryo allantoic fluid-derived [[influenza]] vaccine is developed
 
|-
 
| 1949 || [[John Enders]] cultivates [[poliovirus]] in [[tissue culture]]
 
|-
 
| 1955 || [[Jonas Salk]]'s injectable [[Polio Vaccine|inactivated polio vaccine]] licenced for general use
 
|-
 
| 1960 || Trials of [[Albert Sabin]]'s oral [[Polio vaccine|live attenuated polio vaccine]] begin in USA
 
|-
 
| 1960–1969 || Live attenuated vaccines developed for [[Measles]], [[Mumps]], and [[Rubella]]
 
|-
 
| 1974–1984 || Polysaccharide vaccines for [[Meningococcus]], [[Pneumococcus]], and [[Hemophilus]] are developed
 
|-
 
| 1980 || [[World Health Organization]] declares global eradication of [[smallpox]]
 
|-
 
| 1981 || [[Hepatitis B]] vaccine is licenced
 
|-
 
| 1983 || [[Hemophilus influenzae]] carbohydrate-protein conjugate is developed
 
|-
 
| 1986 || Yeast-derived recombinant hepatitis B vaccine is licensed
 
|-
 
| 1994 || Polio declared eliminated from Americas
 
|-
 
| 2002 || Polio declared eradicated from Europe
 
|-
 
| 2006 || First [[HPV vaccine]] is licensed
 
|-
 
| 2012 || Polio declared eliminated from India
 
|}
 
 
 
==Society and culture==
 
 
 
===Opposition to vaccination===
 
{{main|Vaccine controversy}}
 
[[File:The cow pock.jpg|thumb|[[James Gillray]], ''The Cow-Pock—or—the Wonderful Effects of the New Inoculation!'' (1802)]]
 
 
 
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 |pmc=1123944 |doi=10.1136/bmj.325.7361.430 |url=http://bmj.bmjjournals.com/cgi/content/full/325/7361/430}}</ref>  Although the benefits of preventing suffering and death from serious [[infectious disease]]s greatly outweigh the risks of rare [[adverse effect (medicine)|adverse effects]] 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> disputes have arisen over the morality, ethics, [[Efficacy|effectiveness]], and safety of vaccination. 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 |year=2007 |isbn=978-1-903933-92-3}}</ref> or that vaccine safety studies are inadequate.<ref name=Halvorsen/> Some religious groups do not allow vaccination,<ref>{{cite journal |author=Sinal SH, Cabinum-Foeller E, Socolar R |title=Religion and medical neglect |journal=South Med J |volume=101 |issue=7 |pages=703–6 |year=2008 |pmid=18580731 |doi=10.1097/SMJ.0b013e31817997c9 }}</ref> and some political groups oppose mandatory vaccination on the grounds of [[Liberty|individual liberty]].<ref name=wolfesharp/> In response, concern has been raised that spreading unfounded information about the medical risks of vaccines increases rates of life-threatening infections, not only in the children whose parents refused vaccinations, but also in other children, perhaps too young for vaccines, who could contract infections from unvaccinated carriers (see [[herd immunity]]).<ref>{{Cite journal | last1 = Omer | first1 = SB | last2 = Salmon | first2 = DA | last3 = Orenstein | first3 = WA | last4 = deHart | first4 = MP | last5 = Halsey | first5 = N | title = Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine-Preventable Diseases | doi = 10.1056/NEJMsa0806477 | journal = New England Journal of Medicine | volume = 360 | issue = 19 | pages = 1981–8 |date=May 2009 | pmid = 19420367 | url = http://www.nejm.org/doi/pdf/10.1056/NEJMsa0806477 | format = PDF }}</ref> Some parents believe vaccinations cause [[autism]], although the scientific consensus has rejected this idea.<ref>{{vcite journal |author=Gross L |title=A broken trust: lessons from the vaccine–autism wars |journal=PLoS Biol |volume=7 |issue=5 |pages=e1000114 |year=2009 |pmid=19478850 |doi=10.1371/journal.pbio.1000114 |url=http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000114 |pmc=2682483 }}</ref> In 2011, [[Andrew Wakefield]], a leading proponent of [[MMR vaccine controversy|one of the main controversies regarding a purported link between autism and vaccines]], was found to have been financially motivated to falsify research data and was subsequently stripped of his medical license.<ref>{{cite news|author=By the CNN Wire Staff |url=http://www.cnn.com/2011/HEALTH/01/05/autism.vaccines/index.html |title=Retracted autism study an 'elaborate fraud,' British journal finds |publisher=CNN.com |date= 2011-01-06|accessdate=2013-04-26}}</ref>
 
 
 
===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 [[biotechnology]] companies have little incentive to develop vaccines for these diseases, because there is little revenue potential. Even in more affluent countries, financial returns are usually minimal and the financial and other risks are great.<ref name='market_return'>{{cite news | first=Jesse L. | last=Goodman | title=Statement by Jesse L. Goodman, M.D., M.P.H. Director Center for Biologics, Evaluation and Research Food and Drug Administration U.S. Department of Health and Human Services on US Influenza Vaccine Supply and Preparations for the Upcoming Influenza Season before Subcommittee on Oversight and Investigations Committee on Energy and Commerce United States House of Representatives | date=2005-05-04 | publisher= | url = http://www.hhs.gov/asl/testify/t050504b.html | accessdate = 2008-06-15 }}</ref>
 
 
 
Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations.<ref>{{Cite journal |author=Olesen OF, Lonnroth A, Mulligan B |title=Human vaccine research in the European Union |journal=Vaccine |year=2009 |volume=27 |issue=5 |pages=640–5 |doi=10.1016/j.vaccine.2008.11.064 |pmid=19059446 }}</ref> Many vaccines have been highly cost effective and beneficial for [[public health]].<ref>{{cite journal|last=Jit|first=Mark|coauthors=Newall, Anthony T.; Beutels, Philippe|title=Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies|journal=Human vaccines & immunotherapeutics|date=1 April 2013|volume=9|issue=4|pages=834–840|doi=10.4161/hv.23637}}</ref> The number of vaccines actually administered has risen dramatically in recent decades.<ref>{{cite journal|last=Newall|first=A.T.|coauthors=Reyes, J.F.; Wood, J.G.; McIntyre, P.; Menzies, R.; Beutels, P.|title=Economic evaluations of implemented vaccination programmes: key methodological challenges in retrospective analyses|journal=Vaccine|date=February 2014|volume=32|issue=7|pages=759–765|doi=10.1016/j.vaccine.2013.11.067}}</ref>  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.{{Citation needed|date=June 2008}}
 
 
 
===Patents===
 
The filing of [[patent]]s on vaccine development processes can also be viewed as an obstacle to the development of new vaccines. Because of the weak protection offered through a patent on 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 |year=2006 |volume=9 |issue=4 |pages=413–25 |doi=10.1111/j.1422-2213.2006.00284.x}}</ref>
 
 
 
==Production==
 
[[File:Preparation of measles vaccines.jpg|thumb|Two workers make openings in chicken eggs in preparation for production of measles vaccine.]]
 
Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either on primary cells such as chicken eggs (e.g., for influenza) or on continuous cell lines such as cultured human cells (e.g., for [[hepatitis A]]).<ref>[http://www.washingtonpost.com/wp-dyn/content/graphic/2009/11/24/GR2009112401834.html "Three ways to make a vaccine"] ''[[The Washington Post]]''</ref> Bacteria are grown in [[bioreactor]]s (e.g., ''[[Haemophilus influenzae]]'' type b). Likewise, a recombinant protein derived from the viruses or bacteria can be generated in yeast, bacteria, or cell cultures. After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response of the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials.<ref>{{cite journal |journal=J Am Pharm Assoc |year=2009 |volume=49 |issue=4 |pages=e87–99 |title=Vaccine supply, demand, and policy: a primer |author=Muzumdar JM, Cline RR |pmid=19589753 |doi=10.1331/JAPhA.2009.09007 }}</ref> Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.<ref name=Bae/>
 
 
 
Vaccine production techniques are evolving. Cultured mammalian cells are expected to become increasingly important, compared to conventional options such as chicken eggs, due to greater productivity and low incidence of problems with contamination. Recombination technology that produces genetically detoxified vaccine is expected to grow in popularity for the production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce the quantities of antigens they contain, and thereby decrease undesirable interactions, by using [[pathogen-associated molecular pattern]]s.<ref name=Bae>{{cite journal |journal=Arch Pharm Res |year=2009 |volume=32 |issue=4 |pages=465–80 |title=Innovative vaccine production technologies: the evolution and value of vaccine production technologies |author=Bae K, Choi J, Jang Y, Ahn S, Hur B |pmid=19407962 |doi=10.1007/s12272-009-1400-1 }}</ref>
 
 
 
In 2010, India produced 60 percent of the world's vaccine worth about $900 million.<ref>{{cite web |url=http://www.antaranews.com/en/news/77598/india-produces-60-percent-of-worlds-vaccines |title=India produces 60 percent of world's vaccines |date=November 15, 2011}}</ref>
 
 
 
===Excipients===
 
Beside the active vaccine itself, the following [[excipient]]s are commonly present in vaccine preparations:<ref name=cdc>{{cite web |url=http://www.cdc.gov/vaccines/vac-gen/additives.htm |author=CDC| title=Ingredients of Vaccines&nbsp;— Fact Sheet|accessdate=december 20, 2009}}</ref>
 
* [[Aluminum]] salts or gels are added as adjuvants. Adjuvants are added to promote an earlier, more potent response, and more persistent immune response to the vaccine; they allow for a lower vaccine dosage.
 
* [[Antibiotic]]s are added to some vaccines to prevent the growth of bacteria during production and storage of the vaccine.
 
* Egg [[protein]] is present in influenza and yellow fever vaccines as they are prepared using chicken eggs. Other proteins may be present.
 
* [[Formaldehyde]] is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted viruses and kill bacteria that might contaminate the vaccine during production.
 
* [[Monosodium glutamate]] (MSG) and 2-[[phenoxyethanol]] are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity.
 
* [[Thimerosal]] is a mercury-containing preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria.
 
 
 
===Role of preservatives===
 
Many vaccines need preservatives to prevent serious adverse effects such as ''[[Staphylococcus]]'' infection, which 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/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228 |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]], [[phenoxyethanol]], and [[formaldehyde]]. Thiomersal is more effective against bacteria, has a 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 |year=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 |doi= 10.2165/00002018-200528020-00001}}</ref> Although [[Thiomersal controversy|controversial claims]] have been made that thiomersal contributes to [[autism spectrum disorder|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= Offit PA | authorlink = Paul Offit |doi=10.1056/NEJMp078187 |pmid=17898096 |url=http://www.nejm.org/doi/pdf/10.1056/NEJMp078187 | format = PDF }}</ref>
 
 
 
==Delivery systems==
 
[[File:VaccineBySandraRugio.jpg|thumb|right|Woman receiving rubella vaccination, Brazil, 2008.]]
 
There are several new delivery systems in development{{When|date=July 2011}} in the hope of making vaccines more efficient to deliver. Possible methods include [[liposome]]s and ''[[ISCOM]]'' (immune stimulating complex).<ref>{{cite journal |author= Morein B, Hu KF, Abusugra I |title= Current status and potential application of ISCOMs in veterinary medicine |journal= Adv Drug Deliv Rev |volume=56 |issue=10 |pages=1367–82 |year=2004 |pmid=15191787 |doi=10.1016/j.addr.2004.02.004}}</ref>
 
 
 
The latest developments{{When|date=July 2011}} in vaccine delivery technologies have resulted in oral vaccines. A polio vaccine was developed and tested by volunteer vaccinations with no formal training; the results were positive in that the ease of the vaccines increased. With an oral vaccine, there is no risk of blood contamination. Oral vaccines are likely to be solid that have proven to be more stable and less likely to freeze;<ref>{{cite book|title =Biotechnology Fundamentals |author= Firdos Alam Khan| publisher=CRC Press| url=http://books.google.co.uk/books?id=-s5oRDUuMSIC&pg=PA270&dq=Oral+vaccines+are+likely+to+be+solid+which+have+proven+to+be+more+stable+and+less+likely+to+freeze&hl=en&sa=X&ei=UQ3LUfGgOaud0wXuz4CgCQ&ved=0CC4Q6AEwAA#v=onepage&q=Oral%20vaccines%20are%20likely%20to%20be%20solid%20which%20have%20proven%20to%20be%20more%20stable%20and%20less%20likely%20to%20freeze&f=false|page =270}}</ref> this stability reduces the need for a "[[cold chain]]": the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, may decrease costs of vaccines. A microneedle approach, which is still in stages of development, uses "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".<ref>{{cite journal |author= Giudice EL, Campbell JD |title= Needle-free vaccine delivery |journal= Adv Drug Deliv Rev |volume=58 |issue=1 |pages=68–89 |year=2006 |pmid=16564111 |doi=10.1016/j.addr.2005.12.003}}</ref>
 
 
 
A nanopatch is a needle-free vaccine delivery system that is under development. A stamp-size patch similar to an [[adhesive bandage]] contains about 20,000 microscopic projections per square inch.<ref>{{cite news|title=Australian scientists develop 'needle-free' vaccination|url=http://www.thehindu.com/sci-tech/health/medicine-and-research/australian-scientists-develop-needlefree-vaccination/article2493365.ece|publisher=[[The Hindu]]|date=28 September 2011|location=Chennai, India}}</ref> When worn on the skin, it will deliver vaccine directly to the skin, which has a higher concentration of immune cells than that in the muscles,{{citation needed|date=May 2012}} where needles and syringes deliver.  It thus increases the effectiveness of the vaccination using a lower amount of vaccine used in traditional syringe delivery system.<ref>{{cite web|title=Needle-free nanopatch vaccine delivery system|url=http://www.news-medical.net/news/20110803/Needle-free-nanopatch-vaccine-delivery-system.aspx|publisher=News Medical|date=3 August 2011}}</ref>
 
 
 
===Plasmids===
 
The use of [[plasmid]]s has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies this approach has failed 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|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|display-authors=1 |isbn=978-1-904455-35-6}}</ref>
 
 
 
==Use in veterinary medicine==
 
{{See also|Influenza vaccine#Flu vaccine for nonhumans|Vaccination of dogs}}
 
[[File:US Navy 060815-N-0411D-018 U.S. Army Veterinarian, Capt Gwynne Kinley of Cape Elizabeth, Maine, immunizes a goat with the help of U.S. Navy Operations Specialist 2nd Class Jessica Silva.jpg|thumb|200px|Goat vaccination against [[sheep pox]] and [[pleural pneumonia]]]]
 
Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans.<ref>{{cite journal | last1 = Patel | pmid = 19402200 | first1 = JR | last2 = Heldens | first2 = JG | title = Immunoprophylaxis against important virus disease of horses, farm animals and birds | journal = Vaccine | volume=27 | issue=12 |date=March 2009 | pages=1797–1810 | doi=10.1016/j.vaccine.2008.12.063}}</ref> Both animals kept as pets and animals raised as livestock are routinely 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]], [[infectious canine hepatitis]], [[adenovirus-2]], [[leptospirosis]], [[bordetella|bordatella]], [[canine parainfluenza virus]], and [[Lyme disease]], among others.
 
 
 
==DIVA vaccines==
 
DIVA (Differentiating Infected from Vaccinated Animals) vaccines make it possible to differentiate between infected and vaccinated animals.
 
 
 
DIVA vaccines carry at least one epitope less than the microorganisms circulating in the field. An accompanying diagnostic test that detects antibody against that epitope allows us to actually make that differentiation.
 
 
 
===The first DIVA vaccines===
 
The first DIVA vaccines (formerly termed [[marker vaccine]]s and since 1999 coined as DIVA vaccines) and companion diagnostic tests have been developed by
 
J.T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands.<ref>{{cite journal |author=Van Oirschot JT, Rziha HJ, Moonen PJ, Pol JM, Van Zaane D |title=Differentiation of serum antibodies from pigs vaccinated or infected with Aujeszky's disease virus by a competitive enzyme immunoassay |journal=The Journal of General Virology |year=1986 |volume=67 |issue=6 |pages=1179–82 |doi=10.1099/0022-1317-67-6-1179}}</ref>
 
<ref>{{cite journal |author=Van Oirschot JT |title=Diva vaccines that reduce virus transmission |journal=Journal of Biotechnology |year=1999 |volume=73 |issue=2–3 |pages=195–205 |doi=10.1016/S0168-1656(99)00121-2 |pmid=10486928}}</ref>
 
They found that some existing vaccines against pseudorabies (also termed Aujeszky’s disease) had deletions in their viral genome (among which the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an ELISA that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed.<ref>{{cite journal |author=Van Oirschot JT, Gielkens ALJ, Moormann RJM, Berns AJM |title=Marker vaccines, virus protein-specific antibody assays and the control of Aujeszky's disease |journal=Veterinary Microbiology |year=1990 |volume=23 |issue=1–4 |pages=85–101 |doi=10.1016/0378-1135(90)90139-M |pmid=2169682}}</ref>
 
Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus 1 infections have been developed.<ref>{{cite journal |author=Van Oirschot JT |title=Diva vaccines that reduce virus transmission |journal=Journal of Biotechnology |year=1999 |volume=73 |issue=2–3 |pages=195–205|doi=10.1016/S0168-1656(99)00121-2 |pmid=10486928}}</ref><ref>{{cite journal |author=Kaashoek MJ, Moerman A, Madic J, Rijsewijk FAM, Quak J, Gielkens ALJ, Van Oirschot JT |title=A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine |journal=Vaccine |year=1994 |volume=12 |issue=5 |pages=439–44 |doi=10.1016/0264-410X(94)90122-8 |pmid=8023552}}</ref>
 
 
 
===Use in practice===
 
The DIVA strategy has been applied in various countries and successfully eradicated pseudorabies virus. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and subsequently the infected pigs were removed from the population. Bovine herpesvirus 1 DIVA vaccines are also widely used in practice.
 
 
 
===Other DIVA vaccines (under development)===
 
Scientists have put and still are putting much effort in applying the DIVA principle to a wide range of infectious diseases, such as, for example, classical swine fever,<ref>{{cite journal |author=Hulst MM, Westra DF, Wensvoort G, Moormann RJM|title=Glycoprotein E1 of hog cholera virus expressed in insect cells protects swine from hog cholera |journal=Journal of Virology |year=1993 |volume=67 |issue=9 |pages=5435–5442 |pmc=237945 |pmid=8350404}}</ref> avian influenza,<ref>{{cite journal |author=Capua I, Terregino C, Cattoli G, Mutinelli F, RodriguezJF |title=Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza |journal=Avian Pathology |year=2003 |volume=32 |issue=1 |pages=47–55 |doi=10.1080/0307945021000070714 |pmid=12745380}}</ref> Actinobacillus pleuropneumonia<ref>{{cite journal |author=Maas A, Meens J, Baltes N, Hennig-Pauka I, Gerlach G-F |title=Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae infection |journal=Vaccine |year=2006 |volume=24 |issue=49 |pages=7226–32 |doi=10.1016/j.vaccine.2006.06.047
 
}}</ref> and Salmonella infections in pigs.<ref>{{cite journal |author=Leyman B, Boyen F, Van Parys A, Verbruggh E, Haesebrouck F, Pasmans F.  |title=Salmonella Typhimurium LPS mutations for use in vaccines allowing differentiation of infected and vaccinated pigs |journal=Vaccine |year=2011 |volume=29 |issue=20 |pages=3679–85 |doi=10.1016/j.vaccine.2011.03.004 |pmid=21419163}}</ref>
 
 
 
==Trends==
 
Vaccine development has several trends:<ref name=Plotkin>{{cite journal |author=Plotkin SA |title=Vaccines: past, present and future |journal=Nat Med |volume=11 |issue=4 Suppl |pages=S5–11 |year=2005 |pmid=15812490 |doi=10.1038/nm1209 }}</ref>
 
* Until recently,{{When|date=July 2011}} most vaccines were aimed at infants and children, but adolescents and adults are increasingly being targeted.<ref name=Plotkin/><ref>{{cite news | author=Carlson B | year=2008 | title=Adults now drive growth of vaccine market | work=Gen. Eng. Biotechnol. News | volume=28 | issue=11 | pages=22–3 | url=http://www.genengnews.com/gen-articles/adults-now-drive-growth-of-vaccine-market/2490/ | deadurl=no | archiveurl=http://archive.is/wO9S5 | archivedate=2013-01-08 }}{{open access}}</ref>
 
* Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.<ref name=Plotkin/> In 2013, Biofarma has released a new product called Pentabio, which is combination vaccine of [[Diphtheria]], [[Tetanus]], [[Pertussis]], [[Hepatitis B]], and [[Haemophilus Influenzae]] Type B for baby/infant of [[Indonesia]] Immunization Program.<ref>{{cite web |url=http://en.acnnewswire.com/press-release/english/13434/bio-farma-urges-oic-countries-to-become-self-reliant-in-vaccine |title=Bio Farma Urges OIC Countries to become Self-Reliant in Vaccine |date=June 18, 2013|accessdate=June 19, 2013}}</ref>
 
* New methods of administering vaccines are being developed,{{When|date=July 2011}} such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.<ref name=Plotkin/>
 
* Vaccines are being designed to stimulate innate immune responses, as well as adaptive.<ref name=Plotkin/>
 
* Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.<ref name=Plotkin/>
 
* Vaccines are being developed to defend against bioterrorist attacks such as anthrax, plague, and smallpox.<ref name=Plotkin/>
 
* Appreciation for sex and pregnancy differences in vaccine responses "might change the strategies used by public health officials".<ref>{{cite journal |author=Klein SL, Jedlicka A, Pekosz A |title=The Xs and Y of immune responses to viral vaccines |journal=Lancet Infect Dis |volume=10 |issue=5 |pages=338–49 |date=May 2010 |pmid=20417416 |doi=10.1016/S1473-3099(10)70049-9 |url=}}</ref>
 
* Scientists are now trying to develop synthetic vaccines by reconstructing the outside structure of a [[virus]].<ref>{{cite web |url=http://www.japantimes.co.jp/news/2013/03/28/world/safer-vaccine-created-without-virus/#.UhTT55JSjNV |title=Safer vaccine created without virus |date=March 28, 2013|accessdate=March 28, 2013}}</ref>
 
Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders.<ref>{{cite journal |author= Spohn G, Bachmann MF |title=Exploiting viral properties for the rational design of modern vaccines |journal= Expert Rev Vaccines |volume=7 |issue=1 |pages=43–54 |year=2008 |pmid=18251693 |doi=10.1586/14760584.7.1.43 }}</ref> For example, the experimental vaccine [[CYT006-AngQb]] has been investigated as a possible treatment for [[hypertension|high blood pressure]].<ref>{{cite journal |author=Samuelsson O, Herlitz H |title=Vaccination against high blood pressure: a new strategy |journal=Lancet |volume=371 |issue=9615 |pages=788–9 |year=2008 |pmid=18328909 |doi=10.1016/S0140-6736(08)60355-4 }}</ref> Factors that have impact on the trends of vaccine development include progress in translatory medicine, [[demographics]], [[Regulatory Science|regulatory science]], political, cultural, and social responses.<ref>{{cite journal |author=Poland GA, Jacobson RM, Ovsyannikova IG |title=Trends affecting the future of vaccine development and delivery: the role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics |journal=Vaccine |year=2009 |volume=27 |issue=25–26 |pages=3240–4 |doi=10.1016/j.vaccine.2009.01.069 |pmc=2693340 |pmid=19200833 }}</ref>
 
 
 
==Research==
 
 
 
More complex plants such as tobacco, potato, tomato, and banana can have genes inserted that cause them to produce vaccines usable for humans.<ref>{{cite journal|last1=Sala|first1=F.|last2=Manuela Rigano|first2=M.|last3=Barbante|first3=A.|last4=Basso|first4=B.|last5=Walmsley|first5=AM|last6=Castiglione|first6=S|journal=Vaccine|date=January 2003|volume=21|issue=7–8|pages=803–8|PMID=23888738|title=Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives}}</ref>
 
 
 
==See also==
 
{{div col|3}}
 
* [[Flying syringe]]
 
* [[Jim (horse)|The Horse Named Jim]]
 
* [[Immunization registry]]
 
* [[Immunotherapy]]
 
* [[List of vaccine ingredients]]
 
* [[List of vaccine topics]]
 
* [[OPV AIDS hypothesis]]
 
* [[Reverse vaccinology]]
 
* [[TA-CD]]
 
* [[Virosome]]
 
{{div col end}}
 
 
 
==References==
 
{{Reflist|colwidth=30em}}
 
 
 
==External links==
 
{{Prone to spam|date=April 2013}}
 
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* {{dmoz|Health/Pharmacy/Drugs_and_Medications/Vaccines_and_Antisera|Vaccines and Antisera}}
 
* [http://www.emro.who.int/entity/vpi/ WHO Vaccine preventable diseases and immunization]
 
* [http://www.historyofvaccines.org/ The History of Vaccines], from the [[College of Physicians of Philadelphia]]
 
* [http://www.conted.ox.ac.uk/courses/professional/staticdetails.php?course=227 University of Oxford Vaccinology Programme: a series of short courses in vaccinology]
 
  
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Latest revision as of 19:56, 6 April 2019

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and keep a record of it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Vaccines can be prophylactic (example: to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g., vaccines against cancer are also being investigated; see cancer vaccine).

The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Edward Jenner to denote cowpox. He used it in 1798 in the long title of his Inquiry into the...Variolae vaccinae...known...[as]...the Cow Pox, in which he described the protective effect of cowpox against smallpox.

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