HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model.

Abstract
Antibodies to both infectious forms of vaccinia virus, the mature virion (MV) and the enveloped virion (EV), as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV protein-encoding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model.
AuthorsClement A Meseda, Joseph Campbell, Arunima Kumar, Alonzo D Garcia, Michael Merchlinsky, Jerry P Weir
JournalPloS one (PLoS One) Vol. 8 Issue 6 Pg. e67984 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23785523 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Smallpox Vaccine
  • Viral Envelope Proteins
Topics
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing (immunology)
  • Antibodies, Viral (immunology)
  • Cell Line
  • Disease Models, Animal
  • Gene Deletion
  • Male
  • Mice
  • Recombination, Genetic
  • Smallpox (mortality, prevention & control)
  • Smallpox Vaccine (administration & dosage, immunology)
  • Vaccination
  • Vaccinia virus (genetics, immunology)
  • Viral Envelope Proteins (genetics, immunology)
  • Virion (genetics, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: