A35R: Safer Poxvirus Vaccine

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A35R: The Gateway to a Safer Poxvirus Vaccine Overview Vaccinia virus, a member of the poxvirus family, is best known for its role in the eradication of smallpox. Outside of smallpox, vaccinia viruses have been used to protect animals and humans against multiple infectious diseases (including monkeypox in humans) and as a cancer treatment. Although vaccinia viruses can elicit a strong host-immune response, questions about the safety and/or efficacy of some of these viruses still remain. Our data show that removal of the A35R gene, which is highly conserved in all poxviruses with a mammalian host range, will give both improved safety and efficacy for many poxvirus based vaccines. Technology Dr. Rachel Dr. Rachel Roper from the Department of Microbiology and Immunology at the Brody School of Medicine at East Carolina University has identified a novel gene called A35R. Removal of the A35R gene leads to a poxvirus vaccine that has improved safety and efficacy.  Thus, this technology is useful for the numerous poxvirus vectors designed to protect against infectious disease and treat cancer. The poxvirus vaccinia virus is well suited for vaccine development but its use is limited due to its virulence. By removing the A35R gene in vaccinia virus, virulence is significantly reduced (1000-fold attenuation) leading to an increase in the safety profile of the poxvirus vaccine. The poxvirus vaccinia MVA (Modified Vaccinia Ankara) is very safe but it cannot replicate well and does not induce strong immune responses.  Deletion of the A35 in this pox virus vector improves immune responses.  Additionally the A35 deletion virus replicates to high titers in mammalian cells (much better than MVA). Advantages Improved Safety Increased Immunogenicity No Reduction in Virus Grwoth Cycle Expanision of the Use of Vaccinia Virus as a Vector Infectious Diseases and Immune Modulation Therapeutic Areas of Interest Zika Virues Ebola Rabies Cancer (Improvement in Vaccine Immunogenicity and Safety) Selected Publications Gwendolyn JB Jones, Corey Boles, and Rachel L. Roper. Raccoonpoxvirus Safety in Immunocompromised and Pregnant Mouse Models.Vaccine, 2014 Jun 30;32(31):3977-81. doi: 10.1016/j. PMID: 24837508 K. E. Rehm and R. L. Roper.2011. Deletion of the A35 gene from Modified Vaccinia Virus Ankara Increases Immunogenicity and Isotype Switching. Vaccine, 29: 3276–3283. PMID: 21352940  K. E. Rehm, R. F. Connor, G. J. B. Jones, K. Yimbu, and R. L. Roper.2010. Vaccinia Virus A35R Inhibits MHC Class II Antigen Presentation. Virol.397:176-186. PMID:19954808 K. E. Rehm, G. J. B. Jones, A. A. Tripp, M. W. Metcalf, and R. L. Roper. 2010. The Poxvirus A35 Protein is an Immunoregulator, J. Virol, 84(1):418-425. PMID: 19828608. Roper, R. L. 2006. Characterization of the Vaccinia Virus A35R Protein and its Role in Virulence. J. Virol. Jan, 80: 306-313. PMID: 16352555 Inventor Profile Dr. Rachel Roper is an associate professor in the Department of Microbiology and Immunology at the Brody School of Medicine at East Carolina University. Her research focuses on viral pathogens and mechanisms of virulence in Poxviruses (relatives of smallpox), and Coronaviruses, which include the human Severe Acute Respiratory Syndrome (SARS) and MERS virus. Both virus groups are of concern in human and veterinary health. Smallpox is a Category A biological disease agent which has been identified by the US Government as a primary bioterrorism/biowarfare threat.