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Bio-Terror Agents

    VACCINIA VIRUS

    BIOTERRORBIBLE.COM: There is an ever expanding list of potential bio-terror agents that could be used in a bio-terror attack, but anthraxsmallpox and flu are the only “threats” the government appears worried about. These 3 agents will likely be used the same way that they were used in the U.S. government bio-terror war-games entitled Dark Winter and Atlantic Storm

    Title: Vaccinia 
    Date: 2012
    Source: 
    Wikipedia

    Abstract: 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 for 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.

    Classification

    Vaccinia infections may be divided into the following types:

    1. Generalized vaccinia
    2. Eczema vaccinatum
    3. Progressive vaccinia (Vaccinia gangrenosum, Vaccinia necrosum)
    4. Roseola vaccinia

    Origin
    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).[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.

    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 varioloa 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 ofCambridge, 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).

    History
    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.

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

    In 1939 Alan Downie showed that the smallpox vaccines being used in the 20th century and cowpox virus were not the same, but some sorts of cousins.

    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.

    Common Strains

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

    1. Western Reserve
    2. Copenhagen
    3. Dryvax (also known as "Wyeth"): the vaccine strain previously used in the United States, produced by Wyeth. It was replaced in 2008 [17] by ACAM2000 (see below), produced by Acambis. It was produced as preparations of calf lymphwhich was freeze-dried and treated with antibiotics.
    4. 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.
    5. 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 (Wikipedia, 2012).