Vaccinia

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Vaccinia virus
A TEM micrograp of "Vaccinia virus" virions
A
virions
Virus classification Edit this classification
(unranked): Virus
Realm: Varidnaviria
Kingdom: Bamfordvirae
Phylum: Nucleocytoviricota
Class: Pokkesviricetes
Order: Chitovirales
Family: Poxviridae
Genus: Orthopoxvirus
Species:
Vaccinia virus
Member viruses[1]
Vaccinia
SpecialtyVirology
TypesProgressive vaccinia

Vaccinia virus (VACV or VV) is a large, complex,

fg.[3] The vaccinia virus is the source of the modern smallpox vaccine, which the World Health Organization (WHO) used to eradicate smallpox in a global vaccination campaign in 1958–1977. Although smallpox no longer exists in the wild, vaccinia virus is still studied widely by scientists as a tool for gene therapy and genetic engineering
.

horsepox, and the cowpox strains found in Great Britain are the least closely related to vaccinia.[6]

Classification of vaccinia infections

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:[7]: 391 

Origin

Vaccinia virus is closely related to the virus that causes

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,[8] and analysis of DNA from an early (1902) sample of smallpox vaccine showed that it was 99.7% similar to horsepox virus.[10]

Virology

Poxviruses are unique among

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).[12] 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
]

Multiplicity reactivation

Vaccinia virus is able to undergo multiplicity reactivation (MR).[13] 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[13] 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,[14] nitrogen mustard,[15] and X-rays or gamma rays.[16] Michod et al.[17] 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(s) needed]

Host resistance

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

  • K3L (P18378) is a protein with
    eukaryotic initiation factor 2 (eIF-2alpha). K3L protein inhibits the action of PKR, an activator of interferons.[18]
  • E3L (P21605) is another protein encoded by Vaccinia. E3L also inhibits PKR activation; and is also able to bind to double stranded RNA.[18]
  • B18R is a protein which serves as an interferon inhibitor in one of Moderna's technologies.[19]

Use as a vaccine

Site of a vaccinia injection, several days later.

Vaccinia virus infection is typically very mild and often does not cause symptoms in healthy individuals, although it may cause rash and

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.[20] The rate of myopericarditis with ACAM2000 is 5.7 per 1,000 of primary vaccinees.[21]

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).[22]

A smallpox vaccine,

2022 monkeypox outbreak.[citation needed
]

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.[24]

History

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.[25] 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.[26] Henry Austin Martin introduced a method for vaccine production from calves.[27]

In 1913, E. Steinhardt, C. Israeli, and R. A. Lambert grew vaccinia virus in fragments of pig corneal tissue culture.[28]

A 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."[29]

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.[5][30]

2000–present

In March 2007, a 2-year-old Indiana boy and his mother contracted a life-threatening vaccinia infection from the boy's father.

intravenous immunoglobulin, cidofovir, and Tecovirimat (ST-246), a (then) experimental drug developed by SIGA Technologies.[32] On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.[31]

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.[33] Further cases—also in patients with a history of eczema—occurred in 2012.[34]

Common strains

This is a list of some of the well-characterized vaccinia strains used for research and vaccination.[citation needed]

See also

References

  1. ^ "ICTV 9th Report (2011) Poxviridae". International Committee on Taxonomy of Viruses (ICTV). Retrieved 17 December 2018.
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  20. ^ "Side Effects of Smallpox Vaccination | Smallpox | CDC". 2017-07-12.
  21. ^ "Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination | Smallpox | CDC". 2022-06-03.
  22. ^ Heilprin, John (1 September 2007). "FDA approves new smallpox vaccine". Houston Chronicle. AP. Retrieved 25 May 2018.
  23. ^ "European public assessment report summary: Imvanex". 2018-09-17.
  24. PMID 14683453
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  26. ^ Tucker, Jonathan B. Scourge: The Once and Future Threat of Smallpox. New York: Grove/Atlantic Inc., 2001.
  27. PMID 32473878
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  29. OCLC 57557385.{{cite book}}: CS1 maint: others (link
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  32. ^ "SIGA's Smallpox Drug Candidate Administered to Critically Ill Human Patient" (Press release). SIGA Technologies. 2007-03-17. Retrieved 2018-07-20.
  33. PMID 20592687
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  35. ^ "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

External links