|This article may contain inappropriate or misinterpreted citations that do not verify the text. (May 2008)|
|A TEM micrograph of Vaccinia virus virions.|
|Group:||Group I (dsDNA)|
|Classification and external resources|
Vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of approximately 5-10 fg. Vaccinia virus is well known for its role as a vaccine (its namesake) that eradicated the smallpox disease, making it the first human disease to be successfully eradicated by science. This endeavour was carried out by the World Health Organization under the Smallpox Eradication Program. Post eradication of smallpox, scientists study Vaccinia virus to use as a tool for delivering genes into biological tissues (gene therapy and genetic engineering).
In the early 21st century, due to concerns about smallpox being used as an agent for bioterrorism, there was renewed interest in studying the Vaccinia virus.
Vaccinia infections may be divided into the following types::391
Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same. The precise origin of vaccinia virus is unknown, however, due to the lack of record-keeping as the virus was repeatedly cultivated and passaged in research laboratories for many decades. 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.
Basic biology 
Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus. 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). 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.
Host resistance 
Vaccinia contains within its genome several proteins that give the virus resistance to interferons. K3L 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 is another protein encoded by Vaccinia. E3L also inhibits PKR activation; and is also able to bind to double stranded RNA.
Use as a vaccine 
A Vaccinia virus infection is very mild and is typically asymptomatic in healthy individuals, but it may cause a mild 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 is still 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 one in one million individuals will develop a fatal response to the vaccination. Currently, the vaccine is only administered to health care workers or research personnel who have a high risk of contracting the variola virus, and to the military personnel of the United States of America. Due to the present threat of smallpox-related bioterrorism, there is a possibility the vaccine may have to be widely administered again in the future. Therefore, scientists are currently developing novel vaccine strategies against smallpox which are safer and much faster to deploy during a bioterrorism event.
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 Acambis of Cambridge, England, and Cambridge, Massachusetts, the U.S. Centers for Disease Control and Prevention stockpiled 192.5 million doses of the new vaccine (see list of common strains below).
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.
The original vaccine for smallpox, and the origin of the idea of vaccination, was Cowpox, reported on by Edward Jenner in 1796. The Latin term used for Cowpox was variola vaccina, essentially a direct translation of "cow-related pox". That term lent its name to the whole idea of vaccination. When it was realized that the virus used in smallpox vaccination was not, or was no longer, the same as the Cowpox virus, the name 'vaccinia' stayed with the vaccine-related virus. (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. 41 Italian children contracted syphilis after being vaccinated by the arm to arm method in 1861.
Recent cases 
In March 2007, a 2-year-old Indiana boy and his mother contracted a life-threatening vaccinia infection from the boy's father. 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 an experimental drug being developed by SIGA Technologies. 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. Further cases—also in patients with a history of eczema—occurred in 2012.
Common strains 
This is a list of some of the well-characterized vaccinia strains used in research and immunizations.
- Western Reserve
- Dryvax (also known as "Wyeth"): the vaccine strain previously used in the United States, produced by Wyeth. It was replaced in 2008  by ACAM2000 (see below), produced by Acambis. It was produced as preparations of calf lymph which was freeze-dried and treated with antibiotics.
- ACAM2000: The current strain in use in the USA, 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: 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.
- Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.
- Johnson, L.; Gupta, A. K.; Ghafoor, A.; Akin, D.; Bashir, R. (2006). "Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy". Sensors and Actuators B Chemical 115 (1): 189–197. doi:10.1016/j.snb.2005.08.047.
- James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- Huygelen C (1996). "Jenner's cowpox vaccine in light of current vaccinology". Verh. K. Acad. Geneeskd. Belg. (in Dutch; Flemish) 58 (5): 479–536; discussion 537–8. PMID 9027132.
- Henderson DA, Moss B (1999) . "Smallpox and Vaccinia". In Plotkin SA, Orenstein WA. Vaccines (3rd ed.). Philadelphia, Pennsylvania: WB Saunders. ISBN 0-7216-7443-7. Retrieved 2007-07-25.
- Tolonen N, Doglio L, Schleich S, Krijnse Locker J (1 July 2001). "Vaccinia Virus DNA Replication Occurs in Endoplasmic Reticulum-enclosed Cytoplasmic Mini-Nuclei". Mol. Biol. Cell 12 (7): 2031–46. PMC 55651. PMID 11452001.
- Smith GL, Vanderplasschen A, Law M (1 December 2002). "The formation and function of extracellular enveloped Vaccinia virus". J. Gen. Virol. 83 (Pt 12): 2915–31. PMID 12466468.
- Davies MV, Chang HW, Jacobs BL, Kaufman RJ (1 March 1993). "The E3L and K3L vaccinia virus gene products stimulate translation through inhibition of the double-stranded RNA-dependent protein kinase by different mechanisms". J. Virol. 67 (3): 1688–92. PMC 237544. PMID 8094759.
- Canadian Press, FDA licenses new vaccine against smallpox; can be produced quickly if needed [dead link]
- Vanderplasschen, A.; Pastoret, P.- P. (2003) The Uses of Poxviruses as Vectors. Current Gene Therapy, Volume 3, Number 6, December 2003 , pp. 583-595(13)
- Tucker, Jonathan B. “Scourge : The Once and Future Threat of Smallpox.” New York: Grove/Atlantic Inc., 2001
- Steinhardt E, Israeli C, Lambert RA (September 1913). "Studies on the cultivation of the virus of vaccinia". J. Inf Dis 13 (2): 294–300. doi:10.1093/infdis/13.2.294. JSTOR 30073371.
- Smith, Geoffrey L. (2004-10-19). Poxvirus strategies to evade the host response to infection. London.
- Centers for Disease Control and Prevention (CDC) (2007). "Household transmission of vaccinia virus from contact with a military smallpox vaccinee—Illinois and Indiana, 2007". Morbidity and Mortality Weekly Report 56 (19): 478–81. PMID 17510612.
- "SIGA’s Smallpox Drug Candidate Administered to Critically Ill Human Patient" (Press release). SIGA Technologies. 2007-03-17. Retrieved 2007-06-05.
- Centers for Disease Control and Prevention (CDC) (2010). "Vaccinia Virus Infection After Sexual Contact with a Military Smallpox Vaccinee—Washington, 2010". Morbidity and Mortality Weekly Report 59 (25): 773–75.
- Centers for Disease Control and Prevention (CDC) (March 2013). "Secondary and tertiary transmission of vaccinia virus after sexual contact with a smallpox vaccinee—San Diego, California, 2012". Morbidity and Mortality Weekly Report 62 (8): 145–7. PMID 23446513.
- "Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine". MMWR Morb. Mortal. Wkly. Rep. 57 (8): 207–8. February 29, 2008.
Further reading 
- Gubser C, Hué S, Kellam P, Smith GL (January 2004). "Poxvirus genomes: a phylogenetic analysis". J Gen Virol 85 (1): 105–17. doi:10.1099/vir.0.19565-0. PMID 14718625.
- Centers for Disease Control and Prevention (CDC) (2007). "Vulvar vaccinia infection after sexual contact with a military smallpox vaccinee—Alaska, 2006". MMWR Morb. Mortal. Wkly. Rep. 56 (17): 417–9. PMID 17476203.
- "Vaccinia virus, complete genome". National Center for Biotechnology Information. Retrieved 2007-07-25.
- Condit RC, Moussatche N, Traktman P. "The Vaccinia Virion: 3D Tour". Retrieved 2007-07-26.
- "Smallpox". Emergency Preparedness & Response. Centers for Disease Control and Prevention. Retrieved 2007-07-26.
- Vaccinia Virus Genomes database search results from the Poxvirus Bioinformatics Resource Center
- Virus Pathogen Database and Analysis Resource (ViPR): Poxviridae