Vaccinia

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. 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 mankind. 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). Moreover, due to recent concerns about smallpox resurfacing as a possible agent for bioterrorism, scientists have renewed their interests in studying Vaccinia virus.

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Origin

Vaccinia virus is closely related to the virus that causes cowpox; historically the two were often considered to be one and the same.^[2] 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.^[3] 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.^[2]

Basic biology

Poxviruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell, outside of the nucleus.^[4] 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).^[5] 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.^[6]

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 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 Inc. of Cambridge, England, and Cambridge, Massachusetts, the U.S. Centers for Disease Control and Prevention stockpiled 192.5 million doses of the new vaccine (derived from the old Dryvax, and made using a pox virus vaccinia).^[7]

History

The original vaccine for smallpox, and the origin of the idea of vaccination, was cowpox, reported on by Edward Jenner in 1796.^[3] 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.)

Recent cases

In March 2007, a 2-year-old Indiana boy and his mother contracted the life-threatening vaccinia infection from the boy's father.^[8] 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.^[9] On April 19, 2007, he was sent home with no after effects except for possible scarring of the skin.^[8]

References

Further reading