Smallpox vaccine - Knowledge

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send to one another to know if any of their family has a mind to have the small-pox. They make parties for this purpose, and when they are met (commonly fifteen or sixteen together) the old woman comes with a nutshell full of the matter of the best sort of small-pox and asks what veins you please to have opened. She immediately rips open that you offer to her with a large needle (which gives you no more pain than a common scratch) and puts into the vein as much venom as can lye upon the head of her needle, and after binds up the little wound with a hollow bit of shell, and in this manner opens four or five veins. … The children or young patients play together all the rest of the day and are in perfect health till the eighth. Then the fever begins to seize them and they keep their beds two days, very seldom three. They have very rarely above twenty or thirty in their faces, which never mark, and in eight days time they are as well as before the illness. … There is no example of any one that has died in it, and you may believe I am very well satisfied of the safety of the experiment since I intend to try it on my dear little son. I am patriot enough to take pains to bring this useful invention into fashion in England, and I should not fail to write to some of our doctors very particularly about it if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue for the good of mankind, but that distemper is too beneficial to them not to expose to all their resentment the hardy wight that should undertake to put an end to it. Perhaps if I live to return I may, however, have courage to war with them.

1558:. However, the Faculty favoured variolation and took no action. John Fewster, a surgeon friend of Jenner's from nearby Thornbury, discussed the possibility of cowpox inoculation at meetings as early as 1765. He may have done some cowpox inoculations in 1796 at about the same time that Jenner vaccinated Phipps. However, Fewster, who had a flourishing variolation practice, may have considered this option but used smallpox instead. He thought vaccination offered no advantage over variolation, but maintained friendly contact with Jenner and certainly made no claim of priority for vaccination when critics attacked Jenner's reputation. It seems clear that the idea of using cowpox instead of smallpox for inoculation was considered, and actually tried in the late 18th century, and not just by the medical profession. Therefore, Jenner was not the first to try cowpox inoculation. However, he was the first to publish his evidence and distribute vaccine freely, provide information on selection of suitable material, and maintain it by arm-to-arm transfer. The authors of the official 1745:. This was a sharpened two-prong fork designed to hold one dose of reconstituted freeze-dried vaccine by capillarity. Easy to use with minimum training, cheap to produce ($ 5 per 1000), using one quarter as much vaccine as other methods, and repeatedly re-usable after flame sterilization, it was used globally in the WHO Smallpox Eradication Campaign from 1968. Rubin estimated that it was used to do 200 million vaccinations per year during the last years of the campaign. Those closely involved in the campaign were awarded the "Order of the Bifurcated Needle". This, a personal initiative by Donald Henderson, was a lapel badge, designed and made by his daughter, formed from the needle shaped to form an "O". This represented "Target Zero", the objective of the campaign. 1465: 1429:

Jenner deliberately inoculated with smallpox virus resisted it. These included the first and last patients in a series of arm-to-arm transfers. He concluded that cowpox inoculation was a safe alternative to smallpox inoculation, but rashly claimed that the protective effect was lifelong. This last proved to be incorrect. Jenner also tried to distinguish between 'True' cowpox which produced the desired result and 'Spurious' cowpox which was ineffective and/or produced severe reaction. Modern research suggests Jenner was trying to distinguish between effects caused by what would now be recognised as non-infectious vaccine, a different virus (e.g.

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short-term storage or transport but increasing use was made of glass capillary tubes for this purpose towards the end of the century. During this period there were no adequate methods for assessing the safety of the vaccine and there were instances of contaminated vaccine transmitting infections such as erysipelas, tetanus, septicaemia and tuberculosis. In the case of arm-to-arm transfer there was also the risk of transmitting syphilis. Although this did occur occasionally, estimated as 750 cases in 100 million vaccinations, some critics of vaccination e.g.

600:(RIVM) on growing the Lister/Elstree strain in rabbit kidney cells and tested it in 45,443 Indonesian children in 1973, with comparable results to the same strain of calf lymph vaccine. Two other cell culture vaccines were developed from the Lister strain in the 2000s: Elstree-BN (Bavarian Nordic) and VV Lister CEP (Chicken Embryo Primary, Sanofi Pasteur). Lister/Elstree-RIVM was stockpiled in the Netherlands, and Elstree-BN was sold to some European countries for stockpiles. However, Sanofi dropped its own vaccine after it acquired Acambis in 2008. 1023: 1406: 1071: 1617:

vaccination, 35 states allowed regulation by local authorities, or had no legislation affecting vaccination, whilst in ten states, including Washington, D.C. and Massachusetts, infant vaccination was compulsory. Compulsory infant vaccination was regulated by only allowing access to school for those who had been vaccinated. Those seeking to enforce compulsory vaccination argued that the public good overrode personal freedom, a view supported by the U.S. Supreme Court in

1550:, observing that the two milkmaids living with his family were immune to smallpox, inoculated his family with cowpox to protect them from smallpox. He attracted a certain amount of local criticism and ridicule at the time then interest waned. Attention was later drawn to Jesty, and he was brought to London in 1802 by critics jealous of Jenner's prominence at a time when he was applying to Parliament for financial reward. During 1790–92 Peter Plett, a teacher from 484: 1047: 1715:

vaccine was 100% effective when reconstituted after 6 months storage at 37 °C (99 °F) allowing it to be transported to, and stored in, remote tropical areas. Collier's method was increasingly used and, with minor modifications, became the standard for vaccine production adopted by the WHO Smallpox Eradication Unit when it initiated its global smallpox eradication campaign in 1967, at which time 23 of 59 manufacturers were using the Lister strain.

757:. However, a single-nucleotide deletion truncates membrane protein B5R from a residue length of 317 to 92. Although the truncated protein decreases production of extracellular enveloped virus, animal models have shown that antibodies against other membrane proteins are sufficient for immunity. LC16m8 was approved in Japan in 1975 after testing in over 50,000 children. Vaccination with LC16m8 results in a vaccine "take", but safety is similar to MVA. 1397: 42: 1282: 942: 918: 834:. First-generation vaccines have no specified expiration date and remain viable indefinitely in deep freeze. The U.S. stockpile of WetVax was manufactured in 1956–1957 and maintained since then at −4 °F (−20 °C), and it was still effective when tested in 2004. Replicating vaccines also remain effective even at 1:10 dilution, so a limited number of doses can be stretched to cover a much larger population. 892: 860: 976: 999: 1352: 786:(CDC), "within 3 days of being exposed to the virus, the vaccine might protect you from getting the disease. If you still get the disease, you might get much less sick than an unvaccinated person would. Within 4 to 7 days of being exposed to the virus, the vaccine likely gives you some protection from the disease. If you still get the disease, you might not get as sick as an unvaccinated person would." 1682:

skin of infected calves, was always heavily contaminated and no vaccine was totally free from bacteria. A survey of vaccines in 1900 found wide variations in bacterial contamination. Vaccine issued by the Government Vaccine Establishment contained 5,000 bacteria per gram, while commercial vaccines contained up to 100,000 per gram. The level of bacterial contamination remained unregulated until the

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people at high risk from a replicating vaccine. Japan evaluated MVA and rejected it due to its low immunogenicity, deciding to develop its own attenuated vaccine instead. In the 2000s, MVA was tested in animal models at much higher dosages. When MVA is given to monkeys at 40 times the dosage of Dryvax, it stimulates a more rapid immune response while still causing lesser side effects.

1249:, a man he held as a slave, who – like many of his peers – had been inoculated in Africa before they were kidnapped. This practice was widely criticized at first. However, a limited trial showed six deaths occurred out of 244 who were variolated (2.5%), while 844 out of 5980 died of natural disease (14%), and the process was widely adopted throughout the colonies. 1775:. The last case in the Americas occurred in 1971 (Brazil), south-east Asia (Indonesia) in 1972, and on the Indian subcontinent in 1975 (Bangladesh). After two years of intensive searches, what proved to be the last endemic case anywhere in the world occurred in Somalia, in October 1977. A Global Commission for the Certification of Smallpox Eradication chaired by 1690:. c. 60) set an upper limit of 5,000 per gram, and rejected any batch of vaccine found to contain the causative organisms of erysipelas or wound infections. Unfortunately glycerolated vaccine lost its potency quickly at ambient temperatures which restricted its use in tropical climates. However, it remained in use into the 1970s when a satisfactory 1370:, England as an orphan. As a young child, Jenner was variolated with the other schoolboys through parish funds, but nearly died due to the seriousness of his infection. Fed purgative medicine and going through the bloodletting process, Jenner was put in one of the variolation stables until he recovered. At the age of 13, he was apprenticed to 1155:. In China, powdered smallpox scabs were blown up the noses of the healthy. The patients would then develop a mild case of the disease and from then on were immune to it. The technique did have a 0.5–2.0% mortality rate, but that was considerably less than the 20–30% mortality rate of the disease itself. Two reports on the Chinese practice of 3287: 1401:

offspring become memory T-cells. 5a. Antibodies are produced and destroy the virus. Diagram B: When exposed to the smallpox virus, the immune system is resistant. 1b. Smallpox virus is injected into the bloodstream. 2b. Memory T cells recognize the virus. 3b. Antibodies are produced and destroy the virus.

1210:. Source material tells us on Lady Mary Wortley Montagu; "When Lady Mary was in the Ottoman Empire, she discovered the local practice of inoculation against smallpox called variolation." In 1718 she had her son, aged five variolated. He recovered quickly. She returned to London and had her daughter variolated in 1721 by 1433:/milker's nodes), or contaminating bacterial pathogens. This caused confusion at the time, but would become important criteria in vaccine development. A further source of confusion was Jenner's belief that fully effective vaccine obtained from cows originated in an equine disease, which he mistakenly referred to as 1956:. Five smallpox vaccines manufactured in the United States in 1859–1873 are most similar to each other and horsepox, as well as the 1902 Mulford vaccine. One of the 1859–1873 vaccines was identified as a novel strain of horsepox, containing a complete gene from the 1976 horsepox sample that has deletions in 1832:

to vaccinate 500,000 volunteer health care professionals throughout the country. Recipients were healthcare workers who would be first-line responders in the event of a bioterrorist attack. Many healthcare workers refused or did not pursue vaccination, worried about vaccine side effects, compensation

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c. 49) banned arm-to-arm vaccination, thus preventing transmission of syphilis by this vaccine. However, private practitioners had to purchase vaccine from commercial producers. Although proper use of glycerine reduced bacterial contamination considerably the crude starting material, scraped from the

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by some continental vaccine producers. However, Copeman found that vaccine suspended in 50% chemically pure glycerine and stored under controlled conditions contained very few "extraneous" bacteria and produced satisfactory vaccinations. He later reported that glycerine killed the causative organisms

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in 2001, many governments began building up vaccine stockpiles again for fear of bioterrorism. Several companies sold off their stockpiles of vaccines manufactured in the 1970s, and production of smallpox vaccines resumed. Aventis Pasteur discovered a stockpile from the 1950s and donated it to the US

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lesion can transmit the virus to other people. Rare side effects include postvaccinal encephalitis and myopericarditis. Many countries have stockpiled first generation smallpox vaccines. In a 2006 predictive analysis of casualties if there were a mass vaccination of the populations of Germany and the

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As the oldest vaccine, the smallpox vaccine has gone through several generations of medical technology. From 1796 to the 1880s, the vaccine was transmitted from one person to another through arm-to-arm vaccination. Smallpox vaccine was successfully maintained in cattle starting in the 1840s, and calf

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on 25 September 1806. On 26 August 1807, Bavaria introduced a similar measure. Baden followed in 1809, Prussia in 1815, Württemberg in 1818, Sweden in 1816, England in 1867 and the German Empire in 1874 through the Reichs Vaccination Act. In Lutheran Sweden, the Protestant clergy played a pioneering

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It was an analysis of 23 cases including several individuals who had resisted natural exposure after previous cowpox. It is not known how many Jenner vaccinated or challenged by inoculation with smallpox virus; e.g. Case 21 included 'several children and adults'. Crucially all of at least four whom

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virus on the chorioallantoic membrane of chicken embryos in 1932. The Texas Department of Health began producing egg-based vaccine in 1939 and started using it in vaccination campaigns in 1948. Lederle Laboratories began selling its Avianized smallpox vaccine in the United States in 1959. Egg-based

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In the United States vaccination was regulated by individual states, the first to impose compulsory vaccination being Massachusetts in 1809. There then followed sequences of compulsion, opposition and repeal in various states. By 1930 Arizona, Utah, North Dakota and Minnesota prohibited compulsory

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on the Chinese coast. He returned to Spain in 1806. The vaccine was not carried in the form of flasks, but in the form of 22 orphaned boys, who were 'carriers' of the live cowpox virus. After arrival, "other Spanish governors and doctors used enslaved girls to move the virus between islands, using

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The small-pox so fatal and so general amongst us is here entirely harmless by the invention of ingrafting (which is the term they give it). There is a set of old women who make it their business to perform the operation. Every autumn in the month of September, when the great heat is abated, people

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Diagram A: Exposure to the cowpox virus builds immunity to the smallpox virus. 1a. Cowpox virus is injected into the bloodstream. 2a. The virus enters the cells and a mild fever develops. 3a. T-cells recognize the antigen as a threat. 4a. Activated T-cells replicate, and their

1378:. He observed that people who caught cowpox while working with cattle were known not to catch smallpox. Jenner assumed a causal connection but the idea was not taken up at that time. From 1770 to 1772 Jenner received advanced training in London at St. George's Hospital and as the private pupil of 693:

MVA stimulates the production of fewer antibodies than replicating vaccines. During the smallpox eradication campaign, MVA was considered to be a pre-vaccine that would be administered before a replicating vaccine to reduce the side effects, or an alternative vaccine that could be safely given to

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was available. Animals continued to be widely used by vaccine producers during the smallpox eradication campaign. A WHO survey of 59 producers, some of whom used more than one source of vaccine, found that 39 used calves, 12 used sheep and 6 used water buffalo, whilst only 3 made vaccine in cell

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Until the end of the 19th century, vaccination was performed either directly with vaccine produced on the skin of calves or, particularly in England, with vaccine obtained from the calf but then maintained by arm-to-arm transfer; initially in both cases vaccine could be dried on ivory points for

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examined the evidence from, and visited where necessary, all countries where smallpox had been endemic. In December 1979 they concluded that smallpox had been eradicated; a conclusion endorsed by the WHO General Assembly in May 1980. However, even as the disease was being eradicated there still

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to the liquid vaccine before it was dispensed into ampoules. This protected the virus during the freeze drying process. After drying, the ampoules were sealed under nitrogen. Like other vaccines, once reconstituted it became ineffective after 1–2 days at ambient temperatures. However, the dried

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c. 49) introduced a conscience clause. This allowed exemption on production of a certificate of conscientious objection signed by two magistrates. Such certificates were not always easily obtained and a further act in 1907 allowed exemption by a statutory declaration which could not be refused.

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by growing MVA in cell culture. Unlike replicating vaccines, MVA-BN is administered by injection via the subcutaneous route and does not result in a vaccine "take." A "take" or "major cutaneous reaction" is a pustular lesion or an area of definite induration or congestion surrounding a central

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Stockpiles of newer vaccines must be repurchased periodically since they carry expiration dates. The United States had received 269 million doses of ACAM2000 and 28 million doses of MVA-BN by 2019, but only 100 million doses of ACAM2000 and 65,000 doses of MVA-BN were still available from the

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patients) or history of eczema, and is not considered safe for pregnant women. A woman planning on conceiving should not receive smallpox immunization. Vaccines that only contain attenuated vaccinia viruses (an attenuated virus is one in which the pathogenicity has been decreased through

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To honor Jenner, in 1881 Louis Pasteur proposed at the 7th International Congress of Medicine held in London, to generalize the term "vaccination" to refer to all protective immunization procedures against any infectious diseases and since then we talk about vaccines against different

1231:...scarred the wrists, legs, and forehead of the patient, placed a fresh and kindly pock in each incision and bound it there for eight or ten days, after this time the patient was credibly informed. The patient would then develop a mild case , recover, and thereafter be immune. 1729:

Smallpox vaccine was inoculated by scratches into the superficial layers of the skin, with a wide variety of instruments used to achieve this. They ranged from simple needles to multi-pointed and multi-bladed spring-operated instruments specifically designed for the purpose.

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virus. One-third of first-time vaccinees develop side effects significant enough to miss school, work, or other activities, or have difficulty sleeping. 15–20% of children receiving the vaccine for the first time develop fevers of over 102 °F (39 °C). The

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virus in the skin of live animals. Most first-generation vaccines are calf lymph vaccines that were grown on the skin of cows, but other animals were also used, including sheep. The development of freeze-dried vaccine in the 1950s made it possible to preserve

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in the United States – an indication of rapid spread and deep interest. Despite some concern about the safety of vaccination the mortality using carefully selected vaccine was close to zero, and it was soon in use all over Europe and the United States.

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and liability. Most did not see an immediate need for the vaccine. Some healthcare systems refused to participate, worried about becoming a destination for smallpox patients in the event of an epidemic. Fewer than 40,000 actually received the vaccine.

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The process above shows the steps taken by Edward Jenner to create vaccination. Jenner did this by inoculating James Phipps with cowpox, a similar virus to smallpox, to create immunity, unlike variolation, which used smallpox to create an immunity to

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that is manufactured by Kaketsuken in Japan. Working at the Chiba Serum Institute in Japan, So Hashizume passaged the Lister strain 45 times in primary rabbit kidney cells, interrupting the process after passages 36, 42, and 45 to grow clones on

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Publication of the Inquiry and the subsequent energetic promulgation by Jenner of the idea of vaccination with a virus other than variola virus constituted a watershed in the control of smallpox for which he, more than anyone else deserves the

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were reported (all in first-time vaccinees who received the NYCBOH strain of vaccinia virus), an incidence of 7.8 per 100,000 during the 30 days they were observed. All cases were in young, otherwise healthy adult white men and all survived.

1484:, sailed to spread the vaccine throughout the Spanish Empire, first to the Canary Islands and on to Spanish Central America. While his deputy, José Salvany, took vaccine to the west and east coasts of Spanish South America, Balmis sailed to 1135:" was practiced before the development of a modern vaccine and likely occurred in Africa and China well before the practice arrived in Europe. It may also have occurred in India, but this is disputed; other investigators contend the ancient 4514: 1666:

of erysipelas and tuberculosis when they were added to the vaccine in "considerable quantity", and that his method was widely used on the continent. In 1896, Copeman was asked to supply "extra good calf vaccine" to vaccinate the future

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Horsepox is extinct in the wild, and the only known sample was collected in 1976. Because the sample was collected at the end of the smallpox eradication campaign, scientists considered the possibility that horsepox is a strain of

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lymph vaccine became the leading smallpox vaccine in the 1880s. First-generation vaccines grown on the skin of live animals were widely distributed in the 1950s–1970s to eradicate smallpox. Second-generation vaccines were grown in

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Talbot TR, Stapleton JT, Brady RC, Winokur PL, Bernstein DI, Germanson T, et al. (September 2004). "Vaccination success rate and reaction profile with diluted and undiluted smallpox vaccine: a randomized controlled trial".

1883:, inadequate recordkeeping resulted in the creation of laboratory strains with unclear origins. By the late 19th century, it was unknown whether the vaccine originated from cowpox, horsepox, or an attenuated strain of smallpox. 1875:, after the Latin word for cow. Jenner believed that both cowpox and smallpox were viruses that originated in the horse and passed to the cow, and some doctors followed his reasoning by inoculating their patients directly with 730:

infection. MVA-BN has been approved in the European Union, Canada, and the United States. Clinical trials have found that MVA-BN is safer and just as immunogenic as ACAM2000. This vaccine has also been approved for use against

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infection after being vaccinated with the New York City Board of Health strain. More deaths were predicted for vaccines based other strains: Lister (55.1 Netherlands, 268.5 Germany) and Bern (303.5 Netherlands, 1,381 Germany).

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virus and can cause serious side effects in a small percentage of recipients, including death in 1–10 people per million vaccinations. Third-generation vaccines are much safer due to the milder side effects of the attenuated

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As vaccination spread, some European countries made it compulsory. Concern about its safety led to opposition and then repeal of legislation in some instances. Compulsory infant vaccination was introduced in England by the

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for his views. Reviews of his rejected report, published for the first time in 1999, were skeptical and called for further vaccinations. Additional vaccinations were performed and in 1798 Jenner published his work entitled

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virus. If alcohol is used, it must be allowed to evaporate completely before the vaccine is administered. Vaccination results in a skin lesion that fills with pus and eventually crusts over. This manifestation of localized

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strain that was cloned. However, the use of eggs or cell culture allows for vaccine production in a sterile environment, while first-generation vaccine contains skin bacteria from the animal that the vaccine was grown on.

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published a notice of tender seeking to stockpile 500,000 doses of smallpox vaccine in order to protect against a potential accidental or intentional release of the eradicated virus. On 6 May, the contract was awarded to

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virus had lost over 14% of its genome and could no longer replicate in human cells. MVA was used in West Germany in 1977–1980, but the eradication of smallpox ended the vaccination campaign after only 120,000 doses.

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Jenner sent a paper reporting his observations to the Royal Society in April 1797. It was not submitted formally and there is no mention of it in the Society's records. Jenner had sent the paper informally to

805:, is both safe and effective for use in persons at high risk of exposure to smallpox virus. However, due to the high rate of serious adverse effects, the vaccine will only be made available to the CDC for the 3889: 397:, making it the only human disease to be eradicated. Although routine smallpox vaccination is no longer performed on the general public, the vaccine is still being produced for research, and to guard against 4390: 4327: 4067: 2778: 7147: 752:

and select for pock size. The resulting variant was designated LC16m8 (Lister clone 16, medium pocks, clone 8). Unlike the severely-damaged MVA, LC16m8 contains every gene that is present in the ancestral

1788:, the WHO ensured that known stocks of smallpox virus were either destroyed or moved to safer laboratories. By 1979, only four laboratories were known to have smallpox virus. All English stocks held at 7845:

Unjustified credit is sometimes given to Jenner for introducing the terms virus (already long used to indicate a transmissible poison) and vaccination (introduced by his friend Richard Dunning in 1800.

3761: 1389:" seems to have been a frequent image in the art and literature of this period. But it is known for certain that in the years following 1770, at least six people in England and Germany (Sevel, Jensen, 654: 4607: 3466: 3284:"Emergent Biosolutions' ACAM2000, (Smallpox and Mpox (Vaccinia) Vaccine, Live) Receives U.S. FDA Approval for Mpox Indication; Public Health Mpox Outbreak Continues Across Africa & Other Regions" 1647:

believed that uncontaminated vaccine itself was a cause of syphilis. Smallpox vaccine was the only vaccine available during this period, and so the determined opposition to it initiated a number of

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were isolated from 3,000 doses of Dryvax and found to exhibit significant variation in virulence. The strain with the most similar virulence to the overall Dryvax mixture was selected and grown in

1952:. Modern Brazilian vaccines with a documented introduction date of 1887, made from material collected in an 1866 outbreak of "cowpox" in France, are more similar to horsepox than other strains of 3077:

Ferrier-Rembert A, Drillien R, Meignier B, Garin D, Crance JM (November 2007). "Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate".

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An Inquiry into the Causes and Effects of the Variolae Vaccinae, a disease discovered in some of the western counties of England, particularly Gloucestershire and Known by the Name of Cow Pox.

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matter – the vaccine – with smallpox matter and this essentially produced variolation. Other vaccine material was not reliably derived from cowpox, but from other skin eruptions of cattle.

3585:"A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN) in 56-80-Year-Old Subjects" 5694: 1879:. The situation was further muddied when Louis Pasteur developed techniques for creating vaccines in the laboratory in the late 19th century. As medical researchers subjected viruses to 6392: 7754:"Early smallpox vaccine manufacturing in the United States: Introduction of the "animal vaccine" in 1870, establishment of "vaccine farms", and the beginnings of the vaccine industry" 6954:

Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, et al. (June 2003). "Myopericarditis following smallpox vaccination among vaccinia-naive US military personnel".

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prevented it from being used more widely during the eradication campaign, although no increase in leukemia was seen in Brazil and Sweden despite the presence of ASLV in the chickens.

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strains. Second and third-generation vaccines are still being produced, with manufacturing capacity being built up in the 2000s due to fears of bioterrorism and biological warfare.

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that to honour Jenner the terms be widened to cover the new protective inoculations being introduced. According to some sources the term was first introduced by Jenner's friend

1726:, chief of the Smallpox Eradication Unit from 1967 to 1977 wrote; "Copeman and Collier made an enormous contribution for which neither, in my opinion ever received due credit". 2387:

Anderson MG, Frenkel LD, Homann S, and Guffey J. (2003), "A case of severe monkeypox virus disease in an American child: emerging infections and changing professional values";

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was an early proponent of smallpox vaccination and ordered that army recruits be given the vaccine. Additionally a vaccination program was created for the French Army and his

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or cell cultures for greater purity, and they were used in some areas during the smallpox eradication campaign. Third-generation vaccines are based on attenuated strains of

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gave his children a smallpox vaccination using a serum acquired from Jenner. By 1800, Jenner's work had been published in all the major European languages and had reached

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Vaccine produced by Copeman's method was the only type issued free to public vaccinators by the British Government Vaccine Establishment from 1899. At the same time the

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Varidnaviria > Bamfordvirae > Nucleocytoviricota > Pokkesviricetes > Chitovirales > Poxviridae > Chordopoxvirinae > Orthopoxvirus > Cowpox virus

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Smallpox was eradicated by a massive international search for outbreaks, backed up with a vaccination program, starting in 1967. It was organised and co-ordinated by a

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million doses in 1980, to guard against reemergence of the disease, but 99% of the stockpile was destroyed in the late 1980s when smallpox failed to return. After the

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role in voluntary smallpox vaccination as early as 1800. The first vaccination was carried out in Liechtenstein in 1801, and from 1812 it was mandatory to vaccinate.

3877: 4386: 562:. The second-generation vaccines are also administered through scarification with a bifurcated needle, and they carry the same side effects as the first-generation 4056: 2774: 597: 7137: 4271: 3799: 7648: 1183:. Voltaire does not speculate on where the Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". 3709: 1800:(CDC) in Atlanta, Georgia in 1982, and all South African stocks were destroyed in 1983. By 1984, the only known stocks were kept at the CDC in the U.S. and the 5321:

Michael J. Bennett, War against Smallpox: Edward Jenner and the Global Spread of Vaccination (Cambridge, United Kingdom: Cambridge University Press, 2020), 32.

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Because MVA does not make copies of itself, the team gave it at a higher dose—similar to what's used in the Bavarian Nordic shot today—than the Dryvax vaccine.

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The inoculation technique was documented as having a mortality rate of only one in a thousand. Two years after Kennedy's description appeared, March 1718, Dr.

1226:, the Princess of Wales, allowed Maitland to vaccinate her children. The success of these variolations assured the British people that the procedure was safe. 6767: 4034: 3555: 197: 4603: 3458: 3261: 1437:. This was criticised at the time but vaccines derived from horsepox were soon introduced and later contributed to the complicated problem of the origin of 1241:

Stimulated by a severe epidemic, variolation was first employed in North America in 1721. The procedure had been known in Boston since 1706, when preacher

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Since smallpox has been eradicated, the public is not routinely vaccinated against the disease. The World Health Organization maintained a stockpile of 200

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vaccine was also used widely in Brazil, New Zealand, and Sweden, and on a smaller scale in many other countries. Concerns about temperature stability and

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that had escaped into the wild. However, as more smallpox vaccines were sequenced, older vaccines were found to be more similar to horsepox than modern

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The question of who first tried cowpox inoculation/vaccination cannot be answered with certainty. Most, but still limited, information is available for

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Wiser I, Balicer RD, Cohen D (January 2007). "An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies".

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Among more than 270,000 US military service members vaccinated with smallpox vaccine between December 2002, and March 2003, eighteen cases of probable

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An Essay on External Remedies Wherein it is Considered, Whether all the curable Distempers incident to Human Bodies, may not be cured by Outward Means

3114:"ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense" 1657:, an English Government bacteriologist interested in smallpox vaccine investigated the effects on the bacteria in it of various treatments, including 8992: 7078: 5196: 2857:

Cassimatis DC, Atwood JE, Engler RM, Linz PE, Grabenstein JD, Vernalis MN (May 2004). "Smallpox vaccination and myopericarditis: a clinical review".

2125: 2093: 626:. The United States ordered over 200 million doses of ACAM2000 in 1999–2001 for its stockpile, and production is ongoing to replace expired vaccine. 7362:

Smith GL, Vanderplasschen A (1998). "Extracellular Enveloped Vaccinia virus: Entry, Egress, and Evasion". In Enjuanes L, Siddel SG, Spaan W (eds.).

5591:

Smallpox Vaccine, Ahead of Its Time – How the Late Development of Laboratory Methods and Other Vaccines Affected the Acceptance of Smallpox Vaccine

2155: 1829: 2716: 1385:

Perhaps there was already an informal public understanding of some connection between disease resistance and working with cattle. The "beautiful

7675:"Re-assembly of nineteenth-century smallpox vaccine genomes reveals the contemporaneous use of horsepox and horsepox-related viruses in the USA" 5702: 8135: 6109: 6086: 4578: 4358: 1695:

culture and 3 in embryonated hens' eggs. English vaccine was occasionally made in sheep during World War I but from 1946 only sheep were used.

6371: 5173: 2550:

Operational framework for the deployment of the World Health Organization Smallpox Vaccine Emergency Stockpile in response to a smallpox event

8024: 681:

on donkeys and cows. The Ankara strain was taken to West Germany in 1953, where Herrlich and Mayr grew it on chorioallantoic membrane at the

105: 3561: 3227: 8175: 8170: 4638: 1912:

genomes and identify their relationships with each other. The horsepox virus was sequenced in 2006 and found to be most closely related to

6922: 4183: 1452:, boyhood friend and medical colleague of Jenner. The first smallpox vaccine in the United States was administered in 1799. The physician 1139:

medical texts of India do not describe these techniques. The first clear reference to smallpox inoculation was made by the Chinese author

5259: 4546: 3921: 2177: 511:

that holds vaccine solution in the fork. The skin should be cleaned with water rather than alcohol, as the alcohol could inactivate the

7917: 7901: 6916: 4985: 4177: 4028: 3703: 3672: 2744: 2280: 1797: 1584:

c. 100). By 1871, parents could be fined for non-compliance, and then imprisoned for non-payment. This intensified opposition, and the

783: 5912: 3368:

Mayr A, Hochstein-Mintzel V, Stickl H (March 1975). "Abstammung, Eigenschaften und Verwendung des attenuierten Vaccinia-Stammes MVA".

1393:

1774, Rendall, Plett 1791) tested successfully the possibility of using the cowpox vaccine as an immunization for smallpox in humans.

5143: 1256:

successfully inoculated the five-year-old son of the British ambassador to the Turkish court under orders from the ambassador's wife

798: 610:, which was acquired by Sanofi Pasteur in 2008, before selling the smallpox vaccine to Emergent Biosolutions in 2017. Six strains of 607: 7866: 6425: 3959: 537:

Netherlands, it was estimated that a total of 9.8 people in the Netherlands and 46.2 people in Germany would die from uncontrolled

5054: 3845: 8572: 1785: 1703: 641:

viruses that are much less virulent and carry lesser side effects. The attenuated viruses may be replicating or non-replicating.

8356: 5088: 4328:"Emergent BioSolutions Awarded 10-Year HHS Contract to Deliver ACAM2000, (Smallpox (Vaccinia) Vaccine, Live) Into the Strategic" 4304: 2239: 2209: 389:

virus. Cowpox served as a natural vaccine until the modern smallpox vaccine emerged in the 20th century. From 1958 to 1977, the

8185: 1837: 1147:(痘疹心法) published in 1549. Inoculation for smallpox does not appear to have been widespread in China until the reign era of the 682: 6102:"Zum 200. Geburtstag von Landesphysikus Gebhard Schaedler. Ein Liechtensteinischer Artzt als Pionier der Pockenschutzimpfung." 9043: 8971: 7862: 7730: 7371: 7223: 7037: 6894: 6839: 6229: 5779: 5751: 5647: 5598: 5123: 4845: 4805: 4726: 2710: 2561: 2412: 782:) have been proposed, but some researchers have questioned the possible effectiveness of such a vaccine. According to the US 466:

All three generations of vaccine are available in stockpiles. First and second-generation vaccines contain live unattenuated

4878: 8577: 5197:"An attempt at a new analysis of the mortality caused by smallpox and of the advantages of inoculation to prevent it. 1766" 504:

virus for long periods of time without refrigeration, leading to the availability of freeze-dried vaccines such as Dryvax.

8609: 8361: 8287: 8140: 5678: 416:

derives from the Latin word for cow, reflecting the origins of smallpox vaccination. Edward Jenner referred to cowpox as

7967: 6106:

Jahrbuch des Historischen Vereins fur das Furstentum Liechtenstein. Historischer Verein fur das Furstentum Liechtenstein

4146: 2832: 618:

cells to make the ACAM1000 vaccine. After a successful phase I trial of ACAM1000, the virus was passaged three times in

9019: 8326: 7959: 4436: 4263: 3955: 3811: 3646: 1741:

Laboratories. Based on initial tests with textile needles with the eyes cut off transversely half-way he developed the

1523: 1445: 726:

to increase the number of available doses. It is safer for immunocompromised patients and those who are at risk from a

7621:"Revisiting Jenner's mysteries, the role of the Beaugency lymph in the evolutionary path of ancient smallpox vaccines" 7620: 7014: 8431: 7252: 7008: 6259: 5626: 4872: 3698: 3334: 7911: 6758: 3311:"Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development" 765:

Vaccinia is infectious, which improves its effectiveness, but causes serious complications for people with impaired

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smallpox deaths accounted for 1.8% of deaths, as opposed to the 4.8% of deaths it accounted for at the time of the

1124: 4022: 8619: 8587: 8582: 8411: 5255:

An inquiry concerning the history of the cowpox, principally with a view to supersede and extinguish the smallpox

3249: 1780:

remained stocks of smallpox virus in many laboratories. Accelerated by two cases of smallpox in 1978, one fatal (

227: 123: 5334:

Bailey I (May 1996). "Edward Jenner (1749–1823): naturalist, scientist, country doctor, benefactor to mankind".

8677: 8282: 7133: 4124:"Vaccinia (smallpox) vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2001" 2029: 1846: 1654: 7895: 2240:"Jynneos- vaccinia virus modified strain ankara-bavarian nordic non-replicating antigen injection, suspension" 1623:

in 1905, a landmark ruling which set a precedent for cases dealing with personal freedom and the public good.

8475: 8180: 6044:

Klein S, Schöneberg I, Krause G (October 2012). "Vom Zwang zur Pockenschutzimpfung zum Nationalen Impfplan".

5420:"Edward Jenner's unpublished cowpox inquiry and the Royal Society: Everard Home's report to Sir Joseph Banks" 1789: 1644: 1325: 6989:

Strom B, Stratton K, Anason AP, Baciu A (2005). "4. Lessons Learned from the Smallpox Vaccination Program".

5235: 4215: 3668: 2051: 7726:

Transactions of the International medical congress, seventh session, held in London, August 2d to 9th, 1881

4219: 3883: 3839: 3255: 3221: 1805: 1706:, developed a method for producing a heat-stable freeze-dried vaccine in powdered form. Collier added 0.5% 1253: 1211: 806: 794: 583: 328: 7068: 6681:

Special Commission (1900). "Report of the Lancet Special Commission on Glycerinated Calf Lymph Vaccines".

4412:

Petersen BW, Damon IK, Pertowski CA, Meaney-Delman D, Guarnizo JT, Beigi RH, et al. (February 2015).

2115: 2083: 1972:(i.e. smallpox of the cow), the term devised by Jenner to denote cowpox and used in the long title of his 1511:, vaccinated after his birth. By 1815 about half of French children were vaccinated and by the end of the 1504: 1464: 2683: 2147: 9121: 9079: 8597: 8034: 8017: 3493:"Rapid protection in a monkeypox model by a single injection of a replication-deficient vaccinia virus" 1481: 570: 8647: 7912:"Interim Clinical Considerations for Use of JYNNEOS Vaccine for Mpox Prevention in the United States" 6482:"The Milroy Lectures on the Natural History of Vaccina: Delivered at the Royal College of Physicians" 4510: 2748: 2692: 2553: 2307: 2276: 1904:

now refers only to the smallpox vaccine, while cowpox no longer has a Latin name. The development of

1768: 1619: 1559: 1367: 1257: 897: 865: 390: 6858:

Rubin BA (May 1980). "A note on the development of the bifurcated needle for smallpox vaccination".

4571: 4354: 420:(smallpox of the cow). The origins of the smallpox vaccine became murky over time, especially after 8602: 8567: 8562: 8557: 6101: 5165: 4057:"Considerations on posology for the use of the vaccine Jynneos/ Imvanex (MVA-BN) against monkeypox" 1314: 749: 649: 555: 456: 434:

was subsequently recognized as a separate viral species. Whole-genome sequencing has revealed that

17: 1812:

research and insurance if some obscure reservoir of natural smallpox is discovered in the future.

428:

demonstrated in 1939 that the modern smallpox vaccine was serologically distinct from cowpox, and

9048: 8981: 8962: 8758: 8730: 8692: 8687: 8667: 8190: 7395: 4299: 3550: 3215: 1905: 1850: 1246: 831: 179: 95: 4630: 9029: 8958: 7952: 6910: 6221: 4718: 4171: 1627: 1186:

Variolation was also practiced throughout the latter half of the 17th century by physicians in

521: 5253: 4539: 3925: 1718:

In a letter about landmarks in the history of smallpox vaccine, written to and quoted from by

1710:

to the vaccine to reduce the number of bacterial contaminants but the key stage was to add 5%

9024: 8858: 8853: 8304: 8250: 8160: 1945: 1648: 1379: 723: 190: 115: 6213: 4710: 3947: 3112:

Monath TP, Caldwell JR, Mundt W, Fusco J, Johnson CS, Buller M, et al. (October 2004).

2272: 1988:, was first used in print by Jenner's friend, Richard Dunning in 1800. Initially, the terms 8907: 8848: 8639: 8277: 8155: 8106: 8073: 8007: 7142: 7073: 5838:

Smith MM (1970). "The 'Real Expedición Marítima de la Vacuna' in New Spain and Guatemala".

3596: 3583:

Greenberg RN, Hay CM, Stapleton JT, Marbury TC, Wagner E, Kreitmeir E, et al. (2016).

3504: 3491:

Earl PL, Americo JL, Wyatt LS, Espenshade O, Bassler J, Gong K, et al. (August 2008).

2945:"Correction: Frequency of Adverse Events after Vaccination with Different Vaccinia Strains" 2577: 2488: 2389: 1674: 1594: 1585: 1577: 1264: 1215: 822: 623: 593: 574: 337: 7426:

Tulman ER, Delhon G, Afonso CL, Lu Z, Zsak L, Sandybaev NT, et al. (September 2006).

5795:

Rusnock A (2009). "Catching cowpox: the early spread of smallpox vaccination, 1798-1810".

5480: 5139: 2210:"ACAM2000 (smallpox- vaccinia vaccine, live injection, powder, lyophilized, for solution)" 1753: 1604: 1267:

to Sarah Chiswell, dated 1 April 1717, from the Turkish Embassy describes this treatment:

1128: 8: 8830: 8796: 8682: 8505: 8448: 8443: 8389: 8220: 8088: 8060: 8012: 1974:

An enquiry into the causes and effects of Variolae vaccinae, known by the name of cow pox

1609: 1457: 1223: 8500: 8240: 6597: 6417: 3600: 3508: 2492: 8863: 8697: 8438: 8399: 8384: 8260: 8245: 8230: 8150: 8068: 7831: 7806: 7778: 7753: 7701: 7555: 7506: 7452: 7427: 7347: 7322: 6734: 6709: 6648: 6558: 6534:"Development of Smallpox Vaccine in England in the Eighteenth and Nineteenth Centuries" 6533: 6506: 6481: 6383: 6348: 6335: 6315: 6296: 6183: 6156: 6080: 6026: 5978: 5953: 5907: 5855: 5820: 5528: 5444: 5419: 5395: 5378: 5359: 5227: 5062: 4773: 4748: 4686: 4661: 3833: 3619: 3527: 3434: 3409: 3385: 3345: 3310: 3189: 3138: 3113: 3004: 2987: 2971: 2920: 2628: 2603: 2511: 2457: 2432: 2365: 2340: 1809: 1555: 1430: 1168: 402: 153: 7636: 7529:"The origins and genomic diversity of American Civil War Era smallpox vaccine strains" 6694: 6144: 5890: 5562: 4961: 4936: 2475:

Carroll DS, Emerson GL, Li Y, Sammons S, Olson V, Frace M, et al. (August 2011).

524:

to smallpox. After 2–3 weeks, the scab will fall off and leave behind a vaccine scar.

9126: 8986: 8953: 8786: 8627: 8517: 8406: 8267: 8092: 8055: 7945: 7836: 7783: 7706: 7640: 7601: 7560: 7527:

Duggan AT, Klunk J, Porter AF, Dhody AN, Hicks R, Smith GL, et al. (July 2020).

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Copeman PW (February 1998). "Extinction of the speckled monster celebrated in 1996".

6563: 6511: 6353: 6255: 6225: 6214: 6191: 6148: 6018: 5983: 5894: 5812: 5775: 5747: 5674: 5622: 5594: 5566: 5520: 5484: 5449: 5400: 5351: 5304: 5219: 5119: 5084: 4966: 4868: 4841: 4801: 4778: 4722: 4711: 4691: 4484: 4428: 4294: 4138: 4004: 3624: 3532: 3439: 3350: 3330: 3194: 3143: 3094: 3059: 3009: 2925: 2874: 2824: 2706: 2633: 2557: 2516: 2444: 2433:"The Immunological Relationship of the Virus of Spontaneous Cowpox to Vaccinia Virus" 2408: 2370: 1917: 1887: 1784:), caused by an accidental and unexplained containment breach at a laboratory at the 1742: 1687: 1516: 1512: 1477: 1469: 1310: 508: 425: 280: 267: 254: 51: 8932: 7578:

Schrick L, Tausch SH, Dabrowski PW, Damaso CR, Esparza J, Nitsche A (October 2017).

7510: 6030: 5824: 5532: 5363: 3981:

Pittman PR, Hahn M, Lee HS, Koca C, Samy N, Schmidt D, et al. (November 2019).

3878:"FDA approves first live, non-replicating vaccine to prevent smallpox and monkeypox" 3389: 507:

The vaccine is administered by multiple puncture of the skin (scarification) with a

8912: 8897: 8753: 8527: 7826: 7818: 7773: 7765: 7696: 7686: 7632: 7591: 7550: 7540: 7488: 7447: 7439: 7342: 7293: 7192: 7182: 6996: 6963: 6802: 6729: 6721: 6690: 6652: 6632: 6553: 6545: 6501: 6493: 6343: 6327: 6288: 6160: 6140: 6053: 6010: 5973: 5965: 5902: 5886: 5847: 5804: 5558: 5512: 5476: 5439: 5431: 5390: 5343: 5294: 5231: 5211: 4956: 4952: 4948: 4768: 4764: 4760: 4681: 4673: 4476: 3994: 3614: 3604: 3522: 3512: 3429: 3421: 3377: 3340: 3322: 3184: 3174: 3163:"ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile" 3133: 3125: 3086: 3051: 2999: 2966: 2956: 2915: 2905: 2866: 2775:"Six bifurcated needles for smallpox vaccination | Science Museum Group Collection" 2696: 2623: 2615: 2506: 2496: 2452: 2360: 2356: 2352: 2319: 1772: 1723: 1678: 1589: 1581: 1453: 1416: 1341: 1207: 1148: 373:

is used to prevent smallpox infection caused by the variola virus. It is the first

210: 8453: 7769: 7724: 7298: 7281: 6252:

The Vaccination Controversy; the rise, reign and decline of compulsory vaccination

5643: 3983:"Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox" 3425: 3090: 3055: 9093: 8917: 8715: 8522: 8480: 8366: 8346: 8316: 8299: 8225: 8215: 8145: 8084: 8080: 8029: 7213: 6131:

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5112: 4862: 4387:"HHS Orders 2.5 Million More Doses of JYNNEOS Vaccine For Monkeypox Preparedness" 3609: 3584: 3459:"There's a shortage of monkeypox vaccine. Could one dose instead of two suffice?" 3326: 2961: 2944: 2910: 2893: 2501: 2476: 1948:

in 1902 is 99.7% similar to horsepox, closer than any previously known strain of

1842: 1821: 1601:. c. 31) effectively marked the end of compulsory infant vaccination in England. 1324:

During the earlier days of empirical experimentation in 1758, American Calvinist

715: 658: 442:, and the cowpox strains found in Great Britain are the least closely related to 33: 5874: 5283:"An examination of John Fewster's role in the discovery of smallpox vaccination" 1202:

in England, by Emmanuel Timoni, a doctor affiliated with the British Embassy in

377:

to have been developed against a contagious disease. In 1796, British physician

9105: 9054: 8781: 8672: 8632: 8512: 8333: 8272: 7691: 7674: 7545: 7528: 7187: 7170: 7102:"Canada considering smallpox vaccine for monkeypox cases, says Dr. Theresa Tam" 6636: 5516: 5347: 4414:"Clinical guidance for smallpox vaccine use in a postevent vaccination program" 4093:"Protecting you from mpox (monkeypox): information on the smallpox vaccination" 3497:

Proceedings of the National Academy of Sciences of the United States of America

3129: 3026: 2894:"Frequency of adverse events after vaccination with different vaccinia strains" 2870: 1880: 1762: 1734: 1699: 1554:, reported limited results of cowpox inoculation to the Medical Faculty of the 1531: 1438: 1390: 1219: 1218:

to take an interest and a trial of variolation was carried out on prisoners in

1195: 1172: 779: 678: 670: 629:

ACAM2000 was approved for mpox prevention in the United States in August 2024.

394: 6807: 6790: 6725: 6014: 5435: 4823:

Science and Civilization in China: Volume 6, Biology and Biological Technology

4604:"Vaiolo delle scimmie, 'abbiamo 5 milioni dosi di vaccino: pronti se servirà'" 1123:– was very high without vaccination, up to 35% in some outbreaks. A method of 9115: 8937: 8922: 8892: 8887: 8742: 8495: 8490: 8394: 8039: 7822: 7338: 6967: 6941: 6791:"Development of a stable smallpox vaccine: Collier L. J Hyg 1955; 53: 76–101" 5898: 5467:

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reported that variolation induced no reaction in persons who had had cowpox.

1306: 1298: 1293:, a boy of age 8. 14 May 1796. Painting by Ernest Board (early 20th century). 1286: 1242: 1199: 1164: 1160: 1076: 809:. ACAM2000 was approved for medical use in the United States in August 2007. 766: 421: 378: 8294: 7212:

Flint J, Racaniello VR, Rall GF, Hatziioannou T, Skalka AM (7 August 2020).

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The Mistresses of Cliveden. Three centuries of scandal, power and intrigue

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1405: 8801: 8791: 8652: 8458: 8341: 8309: 8235: 8097: 7988: 7980: 7596: 7579: 7443: 7138:"Statement from the Minister of Health on Canada's Response to Monkeypox" 6277:"Class, Gender, and the Conscientious Objector to Vaccination, 1898-1907" 5404: 5085:"Open Collections Program: Contagion, The Boston Smallpox Epidemic, 1721" 2988:"Vaccinal Infection of the Chorio-Allantoic Membrane of the Chick Embryo" 1977: 1793: 1667: 1631: 1535: 1508: 1449: 1337: 1302: 1156: 1132: 1114: 1052: 1028: 483: 7673:

Brinkmann A, Souza AR, Esparza J, Nitsche A, Damaso CR (December 2020).

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The greatest killer : smallpox in history, with a new introduction

5379:"Who discovered smallpox vaccination? Edward Jenner or Benjamin Jesty?" 4902: 4295:"Aventis to Donate Smallpox Vaccine To the U.S. Government's Stockpile" 3381: 3179: 3162: 2701: 2619: 1691: 1543: 1497:

lymph fluid harvested from them to inoculate their local populations".

1371: 1359:

depicting the early controversy surrounding Jenner's vaccination theory

1329: 80: 7888: 7066: 6992:

The Smallpox Vaccination Program: Public Health in an Age of Terrorism

6316:"Compulsory smallpox vaccination; the University City, Missouri, case" 5619:

Jenner's smallpox vaccine; the riddle of vaccinia virus and its origin

2405:

Jenner's Smallpox Vaccine: The Riddle of Vaccinia Virus and Its Origin

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A major contribution to smallpox vaccination was made in the 1960s by

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4216:"Vaccines and Related Biological Products Advisory Committee Meeting" 2810:"Smallpox vaccination and adverse reactions. Guidance for clinicians" 1996:

referred only to smallpox, but in 1881 Louis Pasteur proposed at the

1861:

The origin of the modern smallpox vaccine has long been unclear, but

1489: 1180: 1179:(1742), the Turks derived their use of inoculation from neighbouring 619: 109: 6331: 5851: 5383:

Transactions of the American Clinical and Climatological Association

5215: 4798:

Oriental Medicine: An Illustrated Guide to the Asian Arts of Healing

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distinct from the "spontaneous" cowpox virus. This work established

1808:. These states report that their repositories are for possible anti- 8818: 8811: 8806: 8776: 8532: 8468: 8463: 7106: 7000: 6292: 5939: 4411: 3408:

Kenner J, Cameron F, Empig C, Jobes DV, Gurwith M (November 2006).

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The skin was not disinfected before use as this killed the vaccine.

2022:"ACAM2000 smallpox vaccine (live vaccinia virus) vial with diluent" 1900: 1895: 1891: 1876: 1871: 1862: 1658: 1598: 1551: 1500: 1396: 1386: 1281: 1203: 1176: 1140: 1136: 802: 603: 439: 430: 386: 357: 308: 137: 69: 50:

in a syringe alongside a vial of Dryvax dried smallpox vaccine and

41: 6057: 4577:. Ministère de la Santé et des Solidarités (France). August 2006. 2477:"Chasing Jenner's vaccine: revisiting cowpox virus classification" 797:(FDA) voted unanimously that a new live virus vaccine produced by 8537: 7976: 6940: