Editing Smallpox vaccine (section)

===First-generation===
[[File:Dried smallpox vaccine.jpg|left|thumb|274x274px|Ovine smallpox vaccine, manufactured by growing live ''vaccinia'' in sheep, 1980s<ref>{{Cite web |title=1613.002 {{!}} Collections Online |url=https://collections.thackraymuseum.co.uk/object-1613-002 |access-date=29 May 2024 |website=collections.thackraymuseum.co.uk}}</ref>]]
The first-generation vaccines are manufactured by growing live ''vaccinia'' 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.<ref name="who2017_stockpile"/> The development of freeze-dried vaccine in the 1950s made it possible to preserve ''vaccinia'' virus for long periods of time without refrigeration, leading to the availability of freeze-dried vaccines such as Dryvax.<ref name="belongia2003">{{cite journal | vauthors = Belongia EA, Naleway AL | title = Smallpox vaccine: the good, the bad, and the ugly | journal = Clinical Medicine & Research | volume = 1 | issue = 2 | pages = 87–92 | date = April 2003 | pmid = 15931293 | pmc = 1069029 | doi = 10.3121/cmr.1.2.87 }}</ref><ref name="Fenner_1988"/>{{rp|115}}

The vaccine is administered by multiple puncture of the skin (scarification) with a [[bifurcated needle]] that holds vaccine solution in the fork.<ref name="who1968_instructions">{{cite web |title=Instructions for smallpox vaccination with bifurcated needle |url=https://www.who.int/publications/i/item/instructions-for-smallpox-vaccination-with-bifurcated-needle |publisher=[[World Health Organization]] (WHO) |date=1968 |access-date=3 July 2022 |archive-date=16 March 2022 |archive-url=https://web.archive.org/web/20220316135121/https://www.who.int/publications/i/item/instructions-for-smallpox-vaccination-with-bifurcated-needle |url-status=live }}</ref> The skin should be cleaned with water rather than alcohol,<ref name="who1968_instructions"/> as the alcohol could inactivate the ''vaccinia'' virus.<ref name="Fenner_1988"/>{{rp|292}}<ref>{{cite web |title=Six bifurcated needles for smallpox vaccination {{!}} Science Museum Group Collection |url=https://collection.sciencemuseumgroup.org.uk/objects/co148183/six-bifurcated-needles-for-smallpox-vaccination-vaccination-needle |publisher=Science Museum (London) |quote=The skin was not disinfected before use as this killed the vaccine. |access-date=3 July 2022 |archive-date=20 May 2022 |archive-url=https://web.archive.org/web/20220520165051/https://collection.sciencemuseumgroup.org.uk/objects/co148183/six-bifurcated-needles-for-smallpox-vaccination-vaccination-needle |url-status=live }}</ref> If alcohol is used, it must be allowed to evaporate completely before the vaccine is administered.<ref name="Fenner_1988"/>{{rp|292}} Vaccination results in a skin lesion that fills with pus and eventually crusts over. This manifestation of localized ''vaccinia'' infection is known as a vaccine "take" and [[Correlates of immunity|demonstrates immunity]] to smallpox. After 2–3 weeks, the scab will fall off and leave behind a vaccine scar.<ref name="cono2003">{{cite journal |vauthors=Cono J, Casey CG, Bell DM |title=Smallpox vaccination and adverse reactions. Guidance for clinicians |journal=MMWR. Recommendations and Reports |date=February 2003 |volume=52 |issue=RR-4 |pages=1–28 |url=<!-- Official URL --> https://www.cdc.gov/mmwr/PDF/rr/rr5204.pdf |pmid=12617510 |access-date=11 August 2022 |archive-date=22 March 2022 |archive-url=https://web.archive.org/web/20220322232656/https://www.cdc.gov/mmwr/PDF/rr/rr5204.pdf |url-status=live }}</ref>

First generation vaccines consist of live, unattenuated ''vaccinia'' 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 {{convert|102|F|C}}. The ''vaccinia'' lesion can transmit the virus to other people.<ref name="cono2003"/> Rare side effects include postvaccinal encephalitis and myopericarditis.<ref name="cono2003"/><ref>{{cite journal | vauthors = Cassimatis DC, Atwood JE, Engler RM, Linz PE, Grabenstein JD, Vernalis MN | title = Smallpox vaccination and myopericarditis: a clinical review | journal = Journal of the American College of Cardiology | volume = 43 | issue = 9 | pages = 1503–1510 | date = May 2004 | pmid = 15120802 | doi = 10.1016/j.jacc.2003.11.053 }}</ref> 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 Netherlands, it was estimated that a total of 9.8 people in the Netherlands and 46.2 people in Germany would die from uncontrolled ''vaccinia'' 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).<ref name="kretzschmar-2006">{{cite journal | vauthors = Kretzschmar M, Wallinga J, Teunis P, Xing S, Mikolajczyk R | title = Frequency of adverse events after vaccination with different vaccinia strains | journal = PLOS Medicine | volume = 3 | issue = 8 | pages = e272 | date = August 2006 | pmid = 16933957 | pmc = 1551910 | doi = 10.1371/journal.pmed.0030272 | doi-access = free | title-link = doi }}</ref><ref name="kretzschmar-2006c">{{cite journal | vauthors = Kretzschmar M, Wallinga J, Teunis P, Xing S, Mikolajczyk R |title=Correction: Frequency of Adverse Events after Vaccination with Different Vaccinia Strains |journal=PLOS Medicine |date=3 October 2006 |volume=3 |issue=10 |pages=e429 |doi=10.1371/journal.pmed.0030429 |pmc=1626554 |doi-access = free | title-link = doi }}</ref>