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Vaccinia virus
A TEM micrograph of Vaccinia virus virions.
Virus classification
Group: Group I (dsDNA)
Family: Poxviridae
Genus: Orthopoxvirus
Species: Vaccinia virus
Vaccinia
Classification and external resources
ICD-10 B08.0
ICD-9 051.0
eMedicine med/2356
MeSH D014615

Vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family.[1] It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a weight of approximately 5-10 fg[2]. Vaccinia virus is well-known for its role as a vaccine 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.

Contents

Classification

Vaccinia infections may be divided into the following types:[3]:391

Origin

Vaccinia virus is closely related to the virus that causes Cowpox; historically the two were often considered to be one and the same.[4] 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.[5] 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.[4]

Basic biology

Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus.[6] 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).[7] 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.[8]

Use as a vaccine

Site of a vaccinia injection, several days later.

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 Vaccinia 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).[9]

History

The original vaccine for smallpox, and the origin of the idea of vaccination, was Cowpox, reported on by Edward Jenner in 1796.[5] The Latin term used for Cowpox was variolae vaccinae, 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. [10]

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.[11] 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[12]. On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.[11]

Common strains

This is a list of some of the well-characterized vaccinia strains used in research and immunizations.

  • Western Reserve
  • Copenhagen
  • Dryvax (also known as "Wyeth"): the vaccine strain previously used in the United States, produced by Wyeth. It was replaced in 2008 [13] 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.

References

  1. ^ Ryan KJ, Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. ISBN 0-8385-8529-9.  
  2. ^ Johnson, L. (2006). "Characterization of vaccinia virus particles using microscale silicon cantilever resonators and atomic force microscopy". Sensors and Actuators B Chemical 115: 189–197. doi:10.1016/j.snb.2005.08.047.   edit
  3. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.  
  4. ^ a b Huygelen C (1996). "Jenner's cowpox vaccine in light of current vaccinology" (in Dutch; Flemish). Verh. K. Acad. Geneeskd. Belg. 58 (5): 479–536; discussion 537–8. PMID 9027132.  
  5. ^ a b Henderson DA, Moss B (1999) [1988]. "Smallpox and Vaccinia". in Plotkin SA, Orenstein WA. Vaccines (3rd ed.). Philadelphia, Pennsylvania: WB Saunders. ISBN 0-7216-7443-7. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=vacc.chapter.3. Retrieved 2007-07-25.  
  6. ^ 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. PMID 11452001. http://www.molbiolcell.org/cgi/content/full/12/7/2031.  
  7. ^ 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. http://vir.sgmjournals.org/cgi/content/full/83/12/2915.  
  8. ^ 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. PMID 8094759. PMC 237544. http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=8094759.  
  9. ^ Canadian Press, FDA licenses new vaccine against smallpox; can be produced quickly if needed
  10. ^ Tucker, Jonathan B. “Scourge : The Once and Future Threat of Smallpox.” New York: Grove/Atlantic Inc., 2001
  11. ^ a b 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. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5619a4.htm?s_cid=mm5619a4_e.  
  12. ^ SIGA Technologies (2007-03-17). "SIGA’s Smallpox Drug Candidate Administered to Critically Ill Human Patient". Press release. http://www.siga.com/press/031907.html. Retrieved 2007-06-05.  
  13. ^ "Notice to Readers: Newly Licensed Smallpox Vaccine to Replace Old Smallpox Vaccine". MMWR Morb. Mortal. Wkly. Rep. 57 (08): 207–8. February 29, 2008. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5708a6.htm.  

Further reading

External links


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