In vaccinia virus

In a national survey in the United States conducted after smallpox had been eliminated, there were 66 cases, with no deaths, among Generalized vaccinia - Generalized vaccinia was characterized by a vesicular rash that sometimes covered the entire body.

This usually occurred 6 to 9 days after vaccination. The lesions usually resembled the initial lesion found at the inoculation site, but they sometimes varied in size. Generalized vaccinia was not associated with immunodeficiency. The rash was usually self-limiting and thus, little or no therapy was administered. There were about Postvaccinial encephalitis - Neurological complications were the most serious ones that occurred from vaccination with vaccinia virus.

Postvaccinal encephalitis usually occurred in patients over the age of two. In the United States, there were 12 cases, of which one resulted in death, among the 13 million vaccinees. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

National Center for Biotechnology Information , U. Antiviral Res. Author manuscript; available in PMC Oct 1. Bertram L. Langland , a, c Karen V. Kibler , a Karen L. Denzler , a Stacy D. White , a Susan A. Baskin a, d, e. Jeffrey O. Karen V. Karen L. Stacy D. Susan A. Carole R. Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at Antiviral Res.

See other articles in PMC that cite the published article. Abstract Vaccinia virus VACV has been used more extensively for human immunization than any other vaccine.

Keywords: poxvirus, orthopoxvirus, smallpox, biodefense, vaccinia virus, vaccine vector, vaccination complications, vaccinia E3L. Introduction Vaccination against smallpox, first introduced by Edward Jenner more than years ago, was the single most effective public health intervention in human history. Orthopoxvirus antigenic cross-reactivity and replication strategy The family Poxviridae is divided into 8 genera.

Vaccine development before the global smallpox eradication campaign Historically, the first efforts at immunization against smallpox were practiced as early as CE involving a process known as variolation Radetsky, Table 1 Description of vaccinia virus vaccine generations. Open in a separate window.

First-generation VACV vaccines and global smallpox eradication Humans are the only known natural reservoir for variola virus. Table 2 Adverse events associated with primary vaccinia vaccination Table illustrates NYCBH strain smallpox vaccine adverse event rates from two studies done in Lane et al.

Replication and immunogenicity of wild-type vaccinia viruses The ability of live VACV vaccines to replicate and generate a protective immune response following challenge has been well documented.

Table 4 In vivo replication and protection by VACVs used in murine studies of 1 st , 2 nd , and 4 th generation replicating smallpox vaccines. It is not a vaccine strain.

Second-generation vaccines: new forms of wild-type VACV The use of live animals for the production of vaccine material has changed due to current unacceptability of this process and quality control issues regarding microbial contamination. Third-generation vaccines: attenuation through sequential passage One commonly used technique to attenuate VACVs involves multiple passaging of the wt viruses in tissue culture cells from alternative hosts, which has been shown to alter properties such as viral host range, virulence, and genome composition.

Fourth-generation vaccines: attenuation through genetic engineering With the advances in biotechnology that allow insertion, deletion and interruption of genes in specific genomic sites, targeted attenuation of viruses became a practical goal.

Induces strong cellular immune response. Decreased virulence in normal mice model. Induces strong humoral response and cell-mediated response. No dissemination. Superior virus-specific cellular immune response both qualitatively and quantitatively.

Decreases VACV replication in murine model. Replication-defective avipox virus expressing CD80 can enhance the efficacy of human DCs to activate specific human T-cell populations. Post-exposure vaccination Following September 11, , the potential use of the smallpox virus VARV as a bioterrorism agent was brought into special attention, as it constitutes an ideal terrorist weapon of mass destruction LeDuc et al.

Genetically modified VACVs as vaccines against heterologous agents The eradication of smallpox combined with the advent of genetically engineered recombinant poxvirus technology demonstrated the feasibility of using VACVs to protect against specific pathogens. Conclusion Many of the genetically modified poxviruses are replication-defective, a characteristic which has long been considered critical in developing safe vaccines in an era of immune deficiency resulting from chemotherapy, organ transplant, HIV infection, or other diseases impacting the immune system.

Acknowledgments The authors would like to thank Mike Bray for his helpful editorial comments, encouragement, and patience. Footnotes Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. Virus Res. Protection induced in mice against a lethal orthopox virus by the Lister strain of vaccinia virus and modified vaccinia virus Ankara MVA Vaccine.

Cytokine receptors encoded by poxviruses: a lesson in cytokine biology. Immunol Today. Vaccinia, cowpox, and camelpox viruses encode soluble gamma interferon receptors with novel broad species specificity. J Virol. The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses.

New generation smallpox vaccines: a review of preclinical and clinical data. Rev Med Virol. Antibodies against the extracellular enveloped virus B5R protein are mainly responsible for the EEV neutralizing capacity of vaccinia immune globulin.

Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Modified vaccinia virus Ankara undergoes limited replication in human cells and lacks several immunomodulatory proteins: implications for use as a human vaccine.

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Avian Dis. Deletion of the vaccinia virus growth factor gene reduces virus virulence. Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype. Vaccinia virus tropism for primary hematolymphoid cells is determined by restricted expression of a unique virus receptor.

Differences and similarities in viral life cycle progression and host cell physiology after infection of human dendritic cells with modified vaccinia virus Ankara and vaccinia virus. Rescue of vaccinia virus lacking the E3L gene by mutants of E3L. Reintroduction of gene s into an attenuated deletion mutant of vaccinia virus strain IHD-W. Microb Pathog.

Expression of CCL20 and granulocyte-macrophage colony-stimulating factor, but not Flt3-L, from modified vaccinia virus ankara enhances antiviral cellular and humoral immune responses. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. Deletion of gene A41L enhances vaccinia virus immunogenicity and vaccine efficacy.

Reducing the dose of smallpox vaccine reduces vaccine-associated morbidity without reducing vaccination success rates or immune responses. J Infect Dis. Antibody profiling by proteome microarray reveals the immunogenicity of the attenuated smallpox vaccine modified vaccinia virus ankara is comparable to that of Dryvax. Differential effects of the type I interferons alpha4, beta, and epsilon on antiviral activity and vaccine efficacy.

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Effects of a vaccinia virus expressing IFN-gamma on the post-exposure prophylaxis of a lethal vaccinia virus infection. Construction of a vaccinia virus deficient in the essential DNA repair enzyme uracil DNA glycosylase by a complementing cell line.

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A prospective study of serum antibody and protection against smallpox. Am J Trop Med Hyg. Clonal vaccinia virus grown in cell culture fully protects monkeys from lethal monkeypox challenge. Smallpox vaccination and bioterrorism with pox viruses. Comp Immunol Microbiol Infect Dis.

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Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. Efficacy of a canarypox-vectored recombinant vaccine expressing the hemagglutinin gene of equine influenza H3N8 virus in the protection of ponies from viral challenge.

Am J Vet Res. Yellow fever vaccine. An attenuated LC16m8 smallpox vaccine: analysis of full-genome sequence and induction of immune protection. Can postexposure vaccination against smallpox succeed? Don appropriate PPE. Cover area of the spill with paper towels and apply an EPA registered disinfectant, working from the perimeter towards the center. Allow 30 minutes of contact time before disposal and cleanup of spill materials. Mucous membrane Flush eyes, mouth or nose for 15 minutes at eyewash station.

Survival Outside Host Up to 39 weeks at 6. Minimum PPE Requirements At minimum, personnel are required to don gloves, closed toed shoes, lab coat, and appropriate face and eye protection prior to working with Vaccinia virus. Additional Precautions All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet BSC.

The use of needles, syringes, and other sharp objects should be strictly limited.