Vaccinia#Host resistance

In addition to the morbidity of uncomplicated primary vaccination, transfer of infection to other sites by scratching, and post-vaccinial encephalitis, other complications of vaccinia infections may be divided into the following types:{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}{{Rp|391}}

• Generalized vaccinia
• Eczema vaccinatum
• Progressive vaccinia (vaccinia gangrenosum, vaccinia necrosum)
• Roseola vaccinia

Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same.{{cite journal |author=Huygelen C |title=Jenner's cowpox vaccine in light of current vaccinology |language=nl |journal=Verh. K. Acad. Geneeskd. Belg. |volume=58 |issue=5 |pages=479–536; discussion 537–538 |year=1996 |pmid=9027132 }} The precise origin of vaccinia virus is unknown due to the lack of record-keeping, as the virus was repeatedly cultivated and passaged in research laboratories for many decades.{{cite book | vauthors = Henderson DA, Moss B | veditors = Plotkin SA, Orenstein WA | title = Vaccines | orig-year = 1988 | edition = 3rd | year = 1999 | publisher = WB Saunders | location = Philadelphia, Pennsylvania | isbn = 978-0-7216-7443-8 | chapter = Smallpox and Vaccinia | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3 | access-date = 2017-09-17 | archive-date = 2009-06-01 | archive-url = https://web.archive.org/web/20090601172056/http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3 | url-status = live }} The most common notion is that vaccinia virus, cowpox virus, and variola virus (the causative agent of smallpox) were all derived from a common ancestral virus. There is also speculation that vaccinia virus was originally isolated from horses, and analysis of DNA from an early (1902) sample of smallpox vaccine showed that it was 99.7% similar to horsepox virus.{{cite journal|doi= 10.1056/NEJMc1707600|pmid= 29020595|title= An Early American Smallpox Vaccine Based on Horsepox|journal= New England Journal of Medicine|volume= 377|issue= 15|pages= 1491–1492|year= 2017|last1= Schrick|first1= Livia|last2= Tausch|first2= Simon H|last3= Dabrowski|first3= P. Wojciech|last4= Damaso|first4= Clarissa R|last5= Esparza|first5= José|last6= Nitsche|first6= Andreas|doi-access= free}}

Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus.{{cite journal |vauthors=Tolonen N, Doglio L, Schleich S, Krijnse Locker J |title=Vaccinia Virus DNA Replication Occurs in Endoplasmic Reticulum-enclosed Cytoplasmic Mini-Nuclei |journal=Mol. Biol. Cell |volume=12 |issue=7 |pages=2031–46 |date=1 July 2001|pmid=11452001 |pmc=55651 |doi=10.1091/mbc.12.7.2031 }} Therefore, the large genome is required for encoding various enzymes and proteins involved in viral DNA replication and gene transcription. During its replication cycle, VV produces four infectious forms which differ in their outer membranes: intracellular mature virion (IMV), the intracellular enveloped virion (IEV), the cell-associated enveloped virion (CEV) and the extracellular enveloped virion (EEV).{{cite journal |vauthors=Smith GL, Vanderplasschen A, Law M |title=The formation and function of extracellular enveloped Vaccinia virus |journal=J. Gen. Virol. |volume=83 |issue=Pt 12 |pages=2915–31 |date=1 December 2002 |pmid=12466468 |doi=10.1099/0022-1317-83-12-2915 |doi-access=free }} Although the issue remains contentious, the prevailing view is that the IMV consists of a single lipoprotein membrane, while the CEV and EEV are both surrounded by two membrane layers and the IEV has three envelopes. The IMV is the most abundant infectious form and is thought to be responsible for spread between hosts. On the other hand, the CEV is believed to play a role in cell-to-cell spread and the EEV is thought to be important for long range dissemination within the host organism.{{citation needed|date=May 2021}}

Vaccinia virus is able to undergo multiplicity reactivation (MR).{{cite journal |author=ABEL P |title=Multiplicity reactivation and marker rescue with vaccinia virus |journal=Virology |volume=17 |issue= 4|pages=511–9 |date=August 1962 |pmid=13858909 |doi= 10.1016/0042-6822(62)90150-2}} MR is the process by which two, or more, virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome. Abel found that vaccinia viruses exposed to doses of UV light sufficient to prevent progeny formation when single virus particles infected host chick embryo cells, could still produce viable progeny viruses when host cells were infected by two or more of these inactivated viruses; that is, MR could occur. Kim and Sharp demonstrated MR of vaccinia virus after treatment with UV-light,{{cite journal |vauthors=Sharp DG, Kim KS |title=Multiplicity reactivation and radiation survival of aggregated vaccinia virus. Calculation of plaque titer based on MR and particle aggregation seen in the electron microscope |journal=Virology |volume=29 |issue=3 |pages=359–66 |date=July 1966 |pmid=5922451 |doi= 10.1016/0042-6822(66)90211-X}} nitrogen mustard,{{cite journal |vauthors=Kim KS, Sharp DG |title=Multiplicity reactivation of vaccinia virus particles treated with nitrogen mustard |journal=J. Virol. |volume=1 |issue=1 |pages=45–9 |date=February 1967 |pmid=5623957 |pmc=375503 |doi= 10.1128/JVI.1.1.45-49.1967}} and X-rays or gamma rays.{{cite journal |vauthors=Kim KS, Sharp DG |title=Multiplicity reactivation of gamma- and x-irradiated Vaccinia virus in L cells |journal=Radiat. Res. |volume=33 |issue=1 |pages=30–6 |date=January 1968 |pmid=5634978 |doi= 10.2307/3572239|jstor=3572239 |bibcode=1968RadR...33...30K }} Michod et al.{{cite journal |vauthors=Michod RE, Bernstein H, Nedelcu AM | year = 2008 | title = Adaptive value of sex in microbial pathogens | journal = Infect Genet Evol | volume = 8 | issue = 3| pages = 267–285 | doi = 10.1016/j.meegid.2008.01.002 | pmid=18295550| bibcode = 2008InfGE...8..267M }} reviewed numerous examples of MR in different viruses, and suggested that MR is a common form of sexual interaction in viruses that provides the advantage of recombinational repair of genome damages.{{additional citation needed|date=May 2021}}

Vaccinia contains within its genome genes for several proteins that give the virus resistance to interferons:

• K3L ({{PDBe-KB|P18378}}) is a protein with homology to the protein eukaryotic initiation factor 2 (eIF-2alpha). K3L protein inhibits the action of PKR, an activator of interferons.
• E3L ({{UniProt|P21605}}) is another protein encoded by Vaccinia. E3L also inhibits PKR activation, and is also able to bind to double stranded RNA.{{cite journal |vauthors=Davies MV, Chang HW, Jacobs BL, Kaufman RJ |title=The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms |journal=J. Virol. |volume=67 |issue=3 |pages=1688–1692 |date=1 March 1993|pmid=8094759 |pmc=237544 |doi=10.1128/JVI.67.3.1688-1692.1993 }}
• B18R ({{UniProt|P21076}}) directly binds to type I interferon to abolish its function; in other words it works as a decoy receptor. It is used in bioengineering, for cells with added nucleic acid might otherwise enter an antiviral state that reduces protein output.{{cite journal |last1=Kim |first1=Yuriy G. |last2=Baltabekova |first2=Aliya Zh. |last3=Zhiyenbay |first3=Erzhan E. |last4=Aksambayeva |first4=Altynai S. |last5=Shagyrova |first5=Zhadyra S. |last6=Khannanov |first6=Rinat |last7=Ramanculov |first7=Erlan M. |last8=Shustov |first8=Alexandr V. |title=Recombinant Vaccinia virus-coded interferon inhibitor B18R: Expression, refolding and a use in a mammalian expression system with a RNA-vector |journal=PLOS ONE |date=7 December 2017 |volume=12 |issue=12 |pages=e0189308 |doi=10.1371/journal.pone.0189308|doi-access=free |pmid=29216299 |pmc=5720773 |bibcode=2017PLoSO..1289308K }} It is also used in a Moderna paper to enhance the chance of converting a cell into a induced pluripotent stem cell (iPSC) using mRNA.{{cite journal |doi=10.1016/j.stem.2010.08.012 |title=Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA |year=2010 |last1=Warren |first1=Luigi |last2=Manos |first2=Philip D. |last3=Ahfeldt |first3=Tim |last4=Loh |first4=Yuin-Han |last5=Li |first5=Hu |last6=Lau |first6=Frank |last7=Ebina |first7=Wataru |last8=Mandal |first8=Pankaj K. |last9=Smith |first9=Zachary D. |last10=Meissner |first10=Alexander |last11=Daley |first11=George Q. |last12=Brack |first12=Andrew S. |last13=Collins |first13=James J. |last14=Cowan |first14=Chad |last15=Schlaeger |first15=Thorsten M. |last16=Rossi |first16=Derrick J. |journal=Cell Stem Cell |volume=7 |issue=5 |pages=618–630 |pmid=20888316 |pmc=3656821 }}

Dissemination of vaccinia infection is rare due widespread immunization.{{cite journal |last1=Verardi |first1=Paulo H. |last2=Titong |first2=Allison |last3=Hagen |first3=Caitlin J. |title=A vaccinia virus renaissance: New vaccine and immunotherapeutic uses after smallpox eradication |journal=Human Vaccines & Immunotherapeutics |date=July 2012 |volume=8 |issue=7 |pages=961–970 |doi=10.4161/hv.21080 |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC3495727/ |access-date=19 January 2025|pmc=3495727 }} Immunocompromised patients may be at risk of developing severe infection. The only current FDA-approved treatment is serotherapy (intravenous infusion of anti-anti-vaccinia immunoglobulin).{{cite journal |last1=Link |first1=Ellen K. |last2=Tscherne |first2=Alina |last3=Sutter |first3=Gerd |last4=Smith |first4=Emily R. |last5=Gurwith |first5=Marc |last6=Chen |first6=Robert T. |last7=Volz |first7=Asisa |title=A Brighton collaboration standardized template with key considerations for a benefit/risk assessment for a viral vector vaccine based on a non-replicating modified vaccinia virus Ankara viral vector |journal=Vaccine |date=January 2025 |volume=43 |pages=126521 |doi=10.1016/j.vaccine.2024.126521 |url=https://www.sciencedirect.com/science/article/pii/S0264410X24012039 |access-date=19 January 2025|doi-access=free }}

Image:Smallpox vaccine site.jpg

Vaccinia virus infection is typically very mild and often does not cause symptoms in healthy individuals, although it may cause rash and fever. Immune responses generated from a vaccinia virus infection protects the person against a lethal smallpox infection. For this reason, vaccinia virus was, and still is, being used as a live-virus vaccine against smallpox. Unlike vaccines that use weakened forms of the virus being vaccinated against, the vaccinia virus vaccine cannot cause a smallpox infection because it does not contain the smallpox virus. However, certain complications and/or vaccine adverse effects occasionally arise. The chance of this happening is significantly increased in people who are immunocompromised. Approximately 1 to 2 people out of every 1 million people vaccinated could die as a result of life-threatening reactions to the vaccination.{{cite web |url=https://www.cdc.gov/smallpox/vaccine-basics/vaccination-effects.html |title=Side Effects of Smallpox Vaccination {{!}} Smallpox {{!}} CDC |date=2017-07-12 |access-date=2022-05-25 |archive-date=2022-05-26 |archive-url=https://web.archive.org/web/20220526103938/https://www.cdc.gov/smallpox/vaccine-basics/vaccination-effects.html |url-status=live }} The rate of myopericarditis with ACAM2000 is 5.7 per 1,000 of primary vaccinees.{{cite journal |url=https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm?s_cid=mm7122e1_w |title=Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination {{!}} Smallpox {{!}} CDC |journal=MMWR. Morbidity and Mortality Weekly Report |date=2022-06-03 |volume=71 |doi=10.15585/mmwr.mm7122e1 |last1=Rao |first1=Agam K. |last2=Petersen |first2=B. W. |last3=Whitehill |first3=F. |last4=Razeq |first4=J. H. |last5=Isaacs |first5=S. N. |last6=Merchlinsky |first6=M. J. |last7=Campos-Outcalt |first7=D. |last8=Morgan |first8=R. L. |last9=Damon |first9=I. |last10=Sánchez |first10=P. J. |last11=Bell |first11=B. P. |issue=22 |pages=734–742 |pmid=35653347 |pmc=9169520 |access-date=2022-08-08 |archive-date=2022-08-08 |archive-url=https://web.archive.org/web/20220808033646/https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm?s_cid=mm7122e1_w |url-status=live }}

On September 1, 2007, the U.S. Food and Drug Administration (FDA) licensed a new vaccine ACAM2000 against smallpox which can be produced quickly upon need. Manufactured by Sanofi Pasteur, the U.S. Centers for Disease Control and Prevention stockpiled 192.5 million doses of the new vaccine (see list of common strains below).{{cite news |url=https://www.chron.com/news/nation-world/article/FDA-approves-new-smallpox-vaccine-1833591.php |title=FDA approves new smallpox vaccine |last=Heilprin |first=John |agency=AP |website=Houston Chronicle |date=1 September 2007 |access-date=25 May 2018 |archive-date=26 May 2018 |archive-url=https://web.archive.org/web/20180526185953/https://www.chron.com/news/nation-world/article/FDA-approves-new-smallpox-vaccine-1833591.php |url-status=live }}

A smallpox vaccine, Imvanex, which is based on the Modified vaccinia Ankara strain, was approved by the European Medicines Agency (EMA) in 2013.{{cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002596/human_med_001666.jsp&mid=WC0b01ac058001d124|title=European public assessment report summary: Imvanex|date=2018-09-17|access-date=2014-05-19|archive-date=2018-06-20|archive-url=https://web.archive.org/web/20180620154521/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F002596%2Fhuman_med_001666.jsp&mid=WC0b01ac058001d124|url-status=dead}} This strain has been used in vaccines during the 2022 monkeypox outbreak.{{cn|date=November 2022}}

Vaccinia is also used in recombinant vaccines, as a vector for expression of foreign genes within a host, in order to generate an immune response. Other poxviruses are also used as live recombinant vaccines.{{cite journal |last1=Vanderplasschen |first1=A. |last2=Pastoret |first2=P.-P. |title=The Uses of Poxviruses as Vectors |journal=Current Gene Therapy |volume=3 |number=6 |date=December 2003 |pages=583–595 |doi=10.2174/1566523034578168|pmid=14683453 }}

The original vaccine for smallpox, and the origin of the idea of vaccination, was Cowpox, described by Edward Jenner in 1798. The Latin term used for Cowpox was Variolae vaccinae, Jenner's own translation of "smallpox of the cow". That term lent its name to the whole idea of vaccination.{{cite journal|pmid=9987167|year=1999|last1=Baxby|first1=D| author-link = Derrick Baxby|title=Edward Jenner's Inquiry; a bicentenary analysis|volume=17|issue=4|pages=301–307|journal=Vaccine|doi=10.1016/S0264-410X(98)00207-2}} When it was realized that the virus used in smallpox vaccination was not, or was no longer, the same as cowpox virus, the name 'vaccinia' was used for the virus in smallpox vaccine. (See OED.) Vaccine potency and efficacy prior to the invention of refrigerated methods of transportation was unreliable. The vaccine would be rendered impotent by heat and sunlight, and the method of drying samples on quills and shipping them to countries in need often resulted in an inactive vaccine. Another method employed was the "arm to arm" method. This involved vaccinating an individual then transferring it to another as soon as the infectious pustule forms, then to another, etc. This method was used as a form of living transportation of the vaccine, and usually employed orphans as carriers. However, this method was problematic due to the possibility of spreading other blood diseases, such as hepatitis and syphilis, as was the case in 1861, when 41 Italian children contracted syphilis after being vaccinated by the "arm to arm" method.{{cite book |last=Tucker |first=Jonathan B. |title=Scourge: The Once and Future Threat of Smallpox |place=New York |publisher=Grove/Atlantic Inc. |date=2001}} Henry Austin Martin introduced a method for vaccine production from calves.{{Cite journal|last1=Esparza|first1=José|last2=Lederman|first2=Seth|last3=Nitsche|first3=Andreas|last4=Damaso|first4=Clarissa R.|date=2020-06-19|title=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|journal=Vaccine|volume=38|issue=30|pages=4773–4779|doi=10.1016/j.vaccine.2020.05.037|issn=0264-410X|pmc=7294234|pmid=32473878}}

In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grew vaccinia virus in fragments of pig corneal tissue culture.{{cite journal | vauthors = Steinhardt E, Israeli C, Lambert RA | title = Studies on the cultivation of the virus of vaccinia | journal = J Inf Dis | volume = 13 | issue = 2 | pages = 294–300 | date = September 1913 | doi = 10.1093/infdis/13.2.294 | jstor = 30073371 | url = https://zenodo.org/record/1431761 | access-date = 2019-09-11 | archive-date = 2022-03-31 | archive-url = https://web.archive.org/web/20220331193944/https://zenodo.org/record/1431761 | url-status = live }}File:Smallpox vaccine USP.jpgA paper published in 1915 by Fredrick W. Twort, a student of Willian Bulloch, is considered to be the beginning of modern phage research. He was attempting to grow vaccinia virus on agar media in the absence of living cells when he noted that many colonies of contaminating micrococci grew up and appeared mucoid, watery or glassy, and this transformation could be induced in other colonies by inoculation of the fresh colony with material from the watery colony. Using a microscope, he observed that bacteria had degenerated into small granules that stained red with Giemsa stain. He concluded that "...it [the agent of transformation] might almost be considered as an acute infectious disease of micrococci."{{Cite book|title=Phages : their role in bacterial pathogenesis and biotechnology|date=2005|publisher=ASM Press |editor=Waldor, Matthew K. |editor2=Friedman, David I. |editor3=Adhya, Sankar Lal |isbn=1-55581-307-0|location=Washington, D.C.|oclc=57557385}}

In 1939 Allan Watt Downie showed that the smallpox vaccines being used in the 20th century and cowpox virus were not the same, but were immunologically related.{{cite journal|pmc=2065307|year=1939|last1=Downie|first1=AW|title=The Immunological Relationship of the Virus of Spontaneous Cowpox to Vaccinia Virus|volume=20|issue=2|pages=158–176|journal=British Journal of Experimental Pathology}}{{Cite journal | last1 = Tyrrell | first1 = D. A. J. | last2 = McCarthy | first2 = K. | doi = 10.1098/rsbm.1990.0004 | title = Allan Watt Downie. September 1901 – 26 January 1988 | journal = Biographical Memoirs of Fellows of the Royal Society | volume = 35 | pages = 98–112 | year = 1990 | title-link = Allan Watt Downie | pmid = 11622284 | doi-access = free }}

In March 2007, a 2-year-old Indiana boy and his mother contracted a life-threatening vaccinia infection from the boy's father.{{cite journal |author=Centers for Disease Control and Prevention (CDC) |title=Household transmission of vaccinia virus from contact with a military smallpox vaccinee—Illinois and Indiana, 2007 |journal=Morbidity and Mortality Weekly Report |volume=56 |issue=19 |pages=478–81 |year=2007 |pmid=17510612 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm?s_cid=mm5619a4_e |access-date=2017-09-17 |archive-date=2021-03-10 |archive-url=https://web.archive.org/web/20210310190959/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm?s_cid=mm5619a4_e |url-status=live }} The boy developed the telltale rash over 80 percent of his body after coming into close contact with his father, who was vaccinated for smallpox before being deployed overseas by the United States Army. The United States military resumed smallpox vaccinations in 2002. The child acquired the infection due to eczema, which is a known risk factor for vaccinia infection. The boy was treated with intravenous immunoglobulin, cidofovir, and Tecovirimat (ST-246), a (then) experimental drug developed by SIGA Technologies.{{cite press release | title = SIGA's Smallpox Drug Candidate Administered to Critically Ill Human Patient | publisher = SIGA Technologies | date = 2007-03-17 | url = https://investor.siga.com/node/7346 | access-date = 2018-07-20 | archive-date = 2018-07-20 | archive-url = https://web.archive.org/web/20180720195253/https://investor.siga.com/node/7346 | url-status = dead }} On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.

In 2010, the Centers for Disease Control and Prevention (CDC) reported that a woman in Washington had contracted vaccinia virus infection after digital vaginal contact with her boyfriend, a military member who had recently been vaccinated for smallpox. The woman had a history of childhood eczema, but she had not been symptomatic as an adult. The CDC indicated that it was aware of four similar cases in the preceding 12 months of vaccinia infection after sexual contact with a recent military vaccinee.{{cite journal |author=Centers for Disease Control and Prevention (CDC) |title=Vaccinia Virus Infection After Sexual Contact with a Military Smallpox Vaccinee—Washington, 2010 |journal=Morbidity and Mortality Weekly Report |volume=59 |issue=25 |pages=773–75 |year=2010 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5925a2.htm?s_cid=mm5925a2_w |pmid=20592687 |access-date=2017-09-17 |archive-date=2021-04-23 |archive-url=https://web.archive.org/web/20210423104514/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5925a2.htm?s_cid=mm5925a2_w |url-status=live }} Further cases—also in patients with a history of eczema—occurred in 2012.{{cite journal |author=Centers for Disease Control and Prevention (CDC) |title=Secondary and tertiary transmission of vaccinia virus after sexual contact with a smallpox vaccinee—San Diego, California, 2012 |journal=Morbidity and Mortality Weekly Report |volume=62 |issue=8 |pages=145–7 |date=March 2013 |pmid=23446513 |pmc=4604863 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6208a2.htm |access-date=2017-09-17 |archive-date=2021-03-09 |archive-url=https://web.archive.org/web/20210309193408/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6208a2.htm |url-status=live }}

This is a list of some of the well-characterized vaccinia strains used for research and vaccination.{{citation needed|date=October 2016}}

• Lister (also known as Elstree): the English vaccine strain used by Leslie Collier to develop heat stable vaccine in powdered form. Used as the basis for vaccine production during the World Health Organization Smallpox Eradication Campaign (SEC)
• Dryvax (also known as "Wyeth"): the vaccine strain previously used in the United States, produced by Wyeth. Used in the SEC, it was replaced in 2008{{cite journal |title=Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=57 |issue=8 |pages=207–8 |date=February 29, 2008 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm |access-date=September 17, 2017 |archive-date=May 20, 2022 |archive-url=https://web.archive.org/web/20220520085013/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm |url-status=live }} by ACAM2000 (see below), produced by Acambis. It was produced as preparations of calf lymph which was freeze-dried and treated with antibiotics.
• EM63: Russian strain used in the SEC
• ACAM2000: The current strain in use in the US, produced by Acambis. ACAM2000 was derived from a clone of a Dryvax virus by plaque purification. It is produced in cultures of Vero cells.
• Modified vaccinia Ankara (also known as MVA): a highly attenuated (not virulent) strain created by passaging vaccinia virus several hundred times in chicken embryo fibroblasts. Unlike some other vaccinia strains it does not make immunodeficient mice sick and therefore may be safer to use in humans who have weaker immune systems due to being very young, very old, having HIV/AIDS, etc.
• LC16m8: an attenuated strain developed and currently used in Japan
• CV-1: an attenuated strain developed in the United States and used there in the late 1960s- 1970s
• Western Reserve
• Copenhagen
• Connaught Laboratories (Canada)

• B13R (virus protein)

{{noteslist}}

{{Reflist}}

{{refbegin}}

• {{cite journal | vauthors = Gubser C, Hué S, Kellam P, Smith GL | title = Poxvirus genomes: a phylogenetic analysis | journal = J Gen Virol | date = January 2004 | volume = 85 | issue = 1 | pages = 105–17 | pmid = 14718625 | doi = 10.1099/vir.0.19565-0 | doi-access = free }}
• {{cite journal |author=Centers for Disease Control and Prevention (CDC) |title=Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee—Alaska, 2006 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=56 |issue=17 |pages=417–9 |year=2007 |pmid=17476203 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5617a1.htm |access-date=2017-09-17 |archive-date=2021-06-28 |archive-url=https://web.archive.org/web/20210628144901/https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5617a1.htm |url-status=live }}
• {{cite journal|pmc=4885089|year=2016|last1=Al Ali|first1=S|title=Use of Reporter Genes in the Generation of Vaccinia Virus-Derived Vectors|journal=Viruses|volume=8|issue=5|pages=134|last2=Baldanta|first2=S|last3=Fernández-Escobar|first3=M|last4=Guerra|first4=S|doi=10.3390/v8050134|pmid=27213433|doi-access=free}}
• {{cite journal|pmc=2440811|pmid=18612436|year=2008|last1=Rubins|first1=K. H.|title=Comparative analysis of viral gene expression programs during poxvirus infection: A transcriptional map of the vaccinia and monkeypox genomes|journal=PLOS ONE|volume=3|issue=7|pages=e2628|last2=Hensley|first2=L. E.|last3=Bell|first3=G. W.|last4=Wang|first4=C|last5=Lefkowitz|first5=E. J.|last6=Brown|first6=P. O.|last7=Relman|first7=D. A.|doi=10.1371/journal.pone.0002628|bibcode=2008PLoSO...3.2628R|doi-access=free}}

{{refend}}

• {{cite web | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=18372 | publisher = National Center for Biotechnology Information | title = Vaccinia virus, complete genome | access-date = 2007-07-25}}
• {{ cite web

|vauthors=Condit RC, Moussatche N, Traktman P | title = The Vaccinia Virion: 3D Tour

| url = http://www.vacciniamodel.com

| access-date = 2007-07-26

}}

• {{cite web | title = Smallpox | publisher = Centers for Disease Control and Prevention | url = http://www.bt.cdc.gov/agent/smallpox | work = Emergency Preparedness & Response | access-date = 2007-07-26 | archive-url = https://web.archive.org/web/20070813192027/http://www.bt.cdc.gov/agent/smallpox/ | archive-date = 2007-08-13 | url-status = dead }}
• {{cite web|url=https://www.bbc.com/future/article/20220725-the-mystery-virus-that-protects-against-monkeypox|title=The mystery virus that protects against monkeypox|first=Zaria|last=Gorvett|access-date=26 July 2022}}

{{Medical resources

| ICD11 = {{ICD11|1E73}}

| ICD10 = B08.0

| ICD9 = {{ICD9|051.0}}

| eMedicineSubj = med

| eMedicineTopic = 2356

| MeshID = D014615

| SNOMED CT = 111852003

}}

• [http://www.viprbrc.org/brc/home.do?decorator=pox Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae]

{{Viral cutaneous conditions}}

{{Taxonbar|from=Q1986297}}

{{Authority control}}

Category:Chordopoxvirinae

Category:Virus-related cutaneous conditions

Category:Genetic engineering