Editing Smallpox vaccine (section)

===Second-generation===

The second-generation vaccines consist of live ''vaccinia'' virus grown in the [[chorioallantoic membrane]] or [[cell culture]]. The second-generation vaccines are also administered through scarification with a bifurcated needle, and they carry the same side effects as the first-generation ''vaccinia'' 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.<ref name="who2017_stockpile"/>

[[Ernest William Goodpasture]], [[Alice Miles Woodruff]], and G. John Buddingh grew ''vaccinia'' virus on the chorioallantoic membrane of chicken embryos in 1932.<ref name="goodpasture1932">{{cite journal | vauthors = Goodpasture EW, Woodruff AM, Buddingh GJ | title = Vaccinal Infection of the Chorio-Allantoic Membrane of the Chick Embryo | journal = The American Journal of Pathology | volume = 8 | issue = 3 | pages = 271–282.7 | date = May 1932 | pmid = 19970016 | pmc = 2062681 }}</ref> The Texas Department of Health began producing egg-based vaccine in 1939 and started using it in vaccination campaigns in 1948.<ref name="Fenner_1988"/>{{rp|588}} Lederle Laboratories began selling its Avianized smallpox vaccine in the United States in 1959.<ref>{{cite book |author1=Council on Drugs (American Medical Association) |title=New and Nonofficial Drugs |date=1964 |publisher=Lippincott |page=739}}</ref> Egg-based 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 [[avian sarcoma leukosis virus]] 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.<ref name="Fenner_1988"/>{{rp|588}}

''Vaccinia'' was first grown in cell culture in 1931 by [[Thomas Milton Rivers]]. The WHO funded work in the 1960s at the Dutch [[National Institute for Public Health and the Environment]] (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.<ref name="Fenner_1988"/>{{rp|588–589}} 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).<ref name="who2017_stockpile"/><ref>{{cite journal | vauthors = Wiser I, Balicer RD, Cohen D | title = An update on smallpox vaccine candidates and their role in bioterrorism related vaccination strategies | journal = Vaccine | volume = 25 | issue = 6 | pages = 976–984 | date = January 2007 | pmid = 17074424 | doi = 10.1016/j.vaccine.2006.09.046 }}</ref><ref>{{cite journal | vauthors = Ferrier-Rembert A, Drillien R, Meignier B, Garin D, Crance JM | title = Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate | journal = Vaccine | volume = 25 | issue = 49 | pages = 8290–8297 | date = November 2007 | pmid = 17964011 | doi = 10.1016/j.vaccine.2007.09.050 }}</ref> Lister/Elstree-RIVM was stockpiled in the Netherlands, and Elstree-BN was sold to some European countries for stockpiles.<ref name="who2017_stockpile"/> However, Sanofi dropped its own vaccine after it acquired Acambis in 2008{{cn|date=April 2025}}.

[[ACAM2000]] is a vaccine developed by [[Acambis]], which was acquired by Sanofi Pasteur in 2008, before selling the smallpox vaccine to Emergent Biosolutions in 2017. Six strains of ''vaccinia'' 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 [[MRC-5]] cells to make the ACAM1000 vaccine. After a successful phase I trial of ACAM1000, the virus was passaged three times in [[Vero cell]]s to develop ACAM2000, which entered mass production at [[Baxter International|Baxter]]. The United States ordered over 200 million doses of ACAM2000 in 1999–2001 for its stockpile, and production is ongoing to replace expired vaccine.<ref>{{cite journal | vauthors = Monath TP, Caldwell JR, Mundt W, Fusco J, Johnson CS, Buller M, Liu J, Gardner B, Downing G, Blum PS, Kemp T, Nichols R, Weltzin R | title = ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain)--a second-generation smallpox vaccine for biological defense | journal = International Journal of Infectious Diseases | volume = 8 | issue = Suppl 2 | pages = S31–S44 | date = October 2004 | pmid = 15491873 | pmc = 7110559 | doi = 10.1016/j.ijid.2004.09.002 }}</ref><ref>{{cite journal | vauthors = Nalca A, Zumbrun EE | title = ACAM2000: the new smallpox vaccine for United States Strategic National Stockpile | journal = Drug Design, Development and Therapy | volume = 4 | pages = 71–79 | date = May 2010 | pmid = 20531961 | pmc = 2880337 | doi = 10.2147/dddt.s3687 | doi-access = free | title-link = doi }}</ref>

ACAM2000 was approved for mpox prevention in the United States in August 2024.<ref name="FDA ACAM2000">{{cite web | title=ACAM2000 | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 August 2024 | url=https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000 | access-date=1 September 2024 | archive-date=17 October 2019 | archive-url=https://web.archive.org/web/20191017062633/https://www.fda.gov/vaccines-blood-biologics/vaccines/acam2000 | url-status=dead }}</ref><ref name="FDA PR 20240830">{{cite press release | title=FDA Roundup: August 30, 2024 | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 August 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-roundup-august-30-2024 | access-date=1 September 2024 | archive-date=1 September 2024 | archive-url=https://web.archive.org/web/20240901025048/https://www.fda.gov/news-events/press-announcements/fda-roundup-august-30-2024 | url-status=dead }}</ref><ref>{{cite press release | title=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 | publisher=Emergent Biosolutions | via=GlobeNewswire | date=29 August 2024 | url=https://www.globenewswire.com/en/news-release/2024/08/29/2938196/33240/en/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-Regio.html | access-date=1 September 2024 | archive-date=1 September 2024 | archive-url=https://web.archive.org/web/20240901025044/https://www.globenewswire.com/en/news-release/2024/08/29/2938196/33240/en/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-Regio.html | url-status=live }}</ref>