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Vaccine Detail

IMV-EEV
Vaccine Information
  • Vaccine Name: IMV-EEV
  • Target Pathogen: Variola virus
  • Target Disease: Smallpox
  • Vaccine Ontology ID: VO_0004095
  • Type: Subunit vaccine
  • A33R from Vaccinia virus (strain: WR (Western Reserve)) gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A33R; associates with A36R; involved in CEV-cell adherence and actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • A34R gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A34R; involved in CEV cell adherence and actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • A36R gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A36R; interacts with A33R and used in actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • B5R from Vaccinia virus (strain: WR (Western Reserve)) gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-B5R; required for trans-Golgi/endosomal membrane-wrapping of IMV (NCBI).
    • Detailed Gene Information: Click Here.
  • D8L gene engineering:
    • Type: Protein
    • Description: Infectious intracellular mature virions (IMV), containing a complex core structure and an outer membrane with nonglycosylated viral proteins, are assembled in factory regions within the cytoplasm of vaccinia virus-infected cells. Some IMV migrate out of the factories, become wrapped with an additional double membrane containing viral glycoproteins, and are then transported on microtubules to the periphery of the cell. The outer of the two added membranes fuses with the plasma membrane during exocytosis, and the resulting extracellular particles consist of an IMV surrounded by one extra fragile membrane (Fogg et al., 2004).
    • Detailed Gene Information: Click Here.
  • H3L gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-H3L; involved in IMV maturation (NCBI).
    • Detailed Gene Information: Click Here.
  • L1R from Vaccinia virus (strain: WR (Western Reserve)) gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-L1R; target of neutralizing antibody; S-S bond formation pathw thiol substrate; myristylprotein (NCBI).
    • Detailed Gene Information: Click Here.
  • VACVgp196 gene engineering:
    • Type: Protein
    • Description:
    • Detailed Gene Information: Click Here.
  • VACVgp200 gene engineering:
    • Type: Protein
    • Description: The cell-associated and released extracellular virions (EV) are thought to be largely responsible for direct cell-to-cell and long-range virus spread within a host, respectively (Fogg et al., 2004).
    • Detailed Gene Information: Click Here.
  • Adjuvant: Ribi vaccine adjuvant
  • Adjuvant: QS-21
  • Preparation: Soluble forms of L1, A33, and B5 were purified. Recombinant proteins (10 µg) were diluted in PBS with the adjuvant for a total injection volume of 0.1 ml. Monophosphoryl-lipid A plus trehalose dicorynomycolate emulsion (MPL+TDM) was prepared immediately before each immunization according to manufacturer's instructions (Fogg et al., 2004).
  • Virulence: (Fogg et al., 2004)
  • Description: Both intracellular mature virus (IMV) and EV are infectious, but they contain different viral outer membrane proteins, bind to cells differently and have different requirements for entry. Although the entry process is not well understood, a model consistent with available data is that IMV fuse directly with plasma membrane, whereas EV entry involves endocytosis, low-pH-induced disruption of the outer membrane, and fusion of the exposed IMV with the endosomal membrane. Protein subunit vaccines have been evaluated in mice (Fogg et al., 2004).
    Recombinant proteins of the outer membranes of IMV and EEV forms of vaccinia virus were used individually or in combination to immunize mice before i.n. challenge with a lethal dose of the WR strain of vaccinia virus. Vaccination with the individual proteins afforded partial protection; complete protection was achieved with 3 doses of the 3-protein IMV–EEV combination vaccine (Parrino et al., 2006).
Host Response

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Female 5- to 6-week-old BALB/c mice were purchased from Taconic (Germantown, N.Y.). 15 µg of QS-21 aliquots (2 mg/ml in water) were used for each immunization. Proteins were administered at 3-week intervals. Blood was collected from the tail vein 1 day prior to each immunization.
    One day prior to challenge, serum samples were collected and mice were weighed. On the day of challenge, an aliquot of purified VV-WR was thawed, sonicated, and diluted in PBS. Mice were anesthetized by inhalation of isoflurane and inoculated i.n. with a 20-µl suspension of 1 x 106 or 2 x107 PFU of VV-WR. Mice were weighed daily for 2 w following challenge and were euthanatized when they lost 30% of their initial body weight (Fogg et al., 2004).
  • Persistence: (Fogg et al., 2004)
  • Side Effects: (Fogg et al., 2004)
  • Efficacy: Complete survival was obtained with the combination of all three proteins. Although there is a need for safer vaccines, it is difficult to evaluate their efficacy in the absence of human smallpox or information regarding the correlates of immunity (Fogg et al., 2004).
  • Description: Soluble forms of several vaccinia virus IMV and EV membrane proteins have been engineered to learn more about immunity to poxviruses and to test the proteins as components of a vaccine. The present study involves recombinant L1, A33, and B5 proteins individually or in combinations and then challenged the mice (Fogg et al., 2004).
References
Fogg et al., 2004: Fogg C, Lustig S, Whitbeck JC, Eisenberg RJ, Cohen GH, Moss B. Protective immunity to vaccinia virus induced by vaccination with multiple recombinant outer membrane proteins of intracellular and extracellular virions. Journal of virology. 2004 Oct; 78(19); 10230-7. [PubMed: 15367588 ].
NCBI: Entrez Gene [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene]
Parrino et al., 2006: Parrino J, Graham BS. Smallpox vaccines: Past, present, and future. The Journal of allergy and clinical immunology. 2006 Dec; 118(6); 1320-6. [PubMed: 17157663 ].