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Thomas Jefferson University - James P McGettigan, PhD
James P McGettigan, PhD

Microbiology & Immunology
Thomas Jefferson University
Jefferson Medical College
Department of Microbiology and Immunology
Jefferson Vaccine Center
Research Assistant Professor
Mailing Address
1020 Locust Street, JAH 466
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4629
Fax: 215-923-7144
james.mcgettigan@jefferson.edu
Qualifications
B.S., The Pennsylvania State University, Biology, 1986

Ph.D., Thomas Jefferson University, Microbiology and Molecular Virology, 2002
Expertise and Research Interests
The World Health Organization and the Global Alliance for Vaccines and Immunizations report that almost 27 million people do not receive vaccines that are available and needed. Due to cost, complicated vaccine strategies and lack of availability, over two million deaths occur annually for otherwise preventable disease. Most of these deaths occur in developing countries, where it is clear that novel vaccines are needed. In addition, simple and less expensive vaccination strategies are also desirable for industrialized countries, where health care costs are becoming a major burden on the medical infrastructure. Therefore, it is our goal to create a new class of vaccines that are simple to administer, inexpensive and effective for use in both industrialized and developing countries.

Our laboratory is interested in identifying new vaccine platforms for use against human rabies virus infections. Rabies remains a global public health threat that kills an estimated 40,000 to 70,000 people per year. However, recent studies indicate that human rabies deaths may be up to 100 times higher than officially reported. It is the seventh most important infectious disease world-wide since it largely affects children. In 2006, rabies was the leading cause of death due to an infectious disease in China. Our vaccine is based on recombinant replication-deficient RV-based vectors, in which one of its five essential genes are deleted. These vectors are very safe and highly immunogenic, and may prove effective alternative vaccines against rabies virus. We are also investigating the use of our vaccines against other globally important infectious diseases, such as HIV-1 and influenza virus.

To support our vaccine research, we are investigating host innate and humoral immune responses to viral pathogens. Specifically, we are investigating the role for alternative antibody effector functions in vaccine design. Conventional vaccines work by inducing neutralizing antibodies that prevent infection. However, antibodies exert their anti-viral effects through a variety of mechanisms. Our laboratory is looking at how non-neutralizing antibody exert alternative antibody effector functions that can influence the outcome of vaccination. We can use this knowledge to rationally design future vaccine candidates.


Keywords
rabies virus; vaccines; replication-deficient vectors; innate immunity
Publications
  • McGettigan, J.P. (2010). Experimental Human Rabies Vaccines  An Update. Expert Reviews in Vaccines. Expert Rev Vaccines. Oct;9(10):1177-86.
  • Gomme, E.A., Faul, E.Jj, Flomenberg, P., McGettigan, J.P., and Schnell, M.J. (2010) Characterization of a Single-Cycle Rabies Virus Based Vaccine Vector. J. Virol. Jan 6 (Epub ahead of print)
  • Schnell, M.J., McGettigan, J. P., Wirblich, C., and Papaneri, A. (2010). Cell Biology of Rabies Virus: using stealth to reach the brain. Nature Reviews in Microbiology, 2010 Jan;8(1):51-61.
  • Faul, E. J., Aye, P. P., Papaneri, A. B., Pahar, B., McGettigan, J. P., Schiro, F., Chervoneva, I., Montefiori, D. C., Lackner, A. A., and Schnell, M. J. (2009). Rabies virus-based vaccines induce high levels of neutralizing antibody and potent CD8+ T cells responses that protect rhesus macaques from AIDS-like disease after SIVmac251 challenge. Vaccine. 2009 Dec 11;28(2):299-308.
  • Cenna J., Hunter M., Tan G.S., Papaneri A.B., Ribka E.P., Schnell M.J., Marx P.A., and McGettigan, J.P. Replication-deficient rabies virus-based vaccines are safe and immunogenic in mice and non-human primates. J Infect Dis., 2009 Oct 15;200(8):1251-60
  • Faul EJ, Wanjalla C.N., McGettigan J.P., and Schnell M.J. Interferon-beta expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity. Virology, 2008 Dec 20;382(2):226-38.
  • Cenna J., Tan G.S., Papaneri A.B., Dietzschold B., Schnell M.J., and McGettigan J.P. Immune Modulating Effect by a Phosphoprotein-deleted Rabies Virus Vaccine Vector Expressing Two Copies of the Rabies Virus Glycoprotein Gene. Vaccine, 2008 Nov 25; 26(50):6405:14.
  • Li J., McGettigan J.P., Faber M., Schnell M.J., and Dietzschold B. Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFkappaB signaling pathway. Vaccine, 2008 Jan 17;26(3):419-26.
  • McKenna P.M., Koser M.L., Carlson K.R., Montefiori D.C., Letvin N.L., Papaneri A.B., Pomerantz R.J., Dietzschold B., Silvera P., McGettigan J.P., Schnell M.J. Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease. J Infect Dis. 2007 Apr 1;195(7):980-8.
  • Li J., Faber M, Papaneri A., Faber M.L., McGettigan J.P., Schnell M.J., and Dietzschold B. A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice. Virology, 2006 Dec 5-20;356(1-2):147-54.
  • Smith M.E., Koser M., Xiao S., Siler C., McGettigan J.P., Calkins C., Pomerantz R.J., Dietzschold B., and Schnell M.J. Rabies virus glycoprotein as a carrier for anthrax protective antigen. Virology, 2006 Sep 30;353(2):344-56.
  • Dave R.S., McGettigan J.P., Qureshi T., Schnell M.J., Nunnari G., and Pomerantz R.J. siRNA targeting Vaccinia virus double-stranded RNA binding protein [E3L] exerts potent antiviral effects. Virology, 2006, May 10;348(2):489-97.
  • *McGettigan J.P., Koser M.L., McKenna P.M., Smith M.E., Marvin J.P., Eisenlohr L.C., Dietzschold B., and Schnell M.J. Enhanced Humoral HIV-1-specifc Immune Responses Generated from Recombinant Rhabdoviral-based Vaccine Vectors Co-expressing HIV-1 Proteins and IL-2. Virology, 2006, Jan 20;344(2):363-77.
  • Tan G.S., McKenna P.M., Koser M.L., McGettigan J.P., and Schnell, M.J. Strong Cellular and Humoral Anti-HIV Env Immune Responses Induced by a Heterologous Rhabdoviral Prime-boost Approach, Virology, 2005 Jan 5;331(1):82-93
  • Koser M.L., McGettigan J.P., Tan G.S., Smith M.E., Koprowski H., Dietzschold B., and Schnell M.J. Rabies virus as a carrier for foreign antigens. PNAS, 2004, 22;101(25):9405-10
  • Irie T., Licata J.M., McGettigan J.P., Schnell M.J., and Harty R.N. Budding of PPxY-Containing Rhabdoviruses is not Dependent on Host Proteins TGS101 and VPS4, J. Virol., 2004, 78(6):2657-65
  • McKenna P.M., Pomerantz R.J., Dietzschold B., McGettigan J.P., and Schnell M.J. Covalently linked human immunodeficiency virus type 1 gp120/gp41 is stably anchored in rhabdovirus particles and exposes critical neutralizing epitopes. J Virol., 2003 Dec;77(23):12782-94.
  • McKenna P.M., McGettigan J.P., Dietzschold B., Pomerantz R.J., and Schnell M.J. Recombinant Rhabdoviruses as Potential Vaccines for HIV-1 and other Diseases. Current HIV Research, 2003, 1, 229-237.
  • McGettigan J.P., Naper K., Orenstein J., Koser M., McKenna P.M., and Schnell M.J. Functional human immunodeficiency virus type 1 (HIV-1) Gag-Pol or HIV-1 Gag-Pol and env expressed from a single rhabdovirus-based vaccine vector genome. J Virol. 2003 Oct;77(20):10889-99.
  • McGettigan J.P., Pomerantz R.J., Siler C.A., McKenna P.M., Foley H.D., Dietzschold B., and Schnell M. J. Second-generation rabies virus-based vaccine vectors expressing human immunodeficiency virus type 1 gag have greatly reduced pathogenicity but are highly immunogenic. J. Virol. 2003 77:237-44.
  • Faber M., Pulmanausahakul R., Hodawadekar S.S., Spitsin S., McGettigan J.P., Schnell M.J., and Dietzschold B. Overexpression of the rabies virus glycoprotein results in enhancement of apoptosis and antiviral immune response. J. Virol., 2002, 76, 3374-3381.
  • McGettigan J.P., McKenna P.M., and Schnell M. J. In: HIV-1 Vaccines  The Search Continues. Clin Lab Med., 2002, 22, 799-820. W. B. Saunders, Philadelphia, PA, USA.
  • Siler C.A., McGettigan J.P., Dubuisson J., Herrine S.K., Pomerantz R.J, and Schnell M.J. Killed and live-viral Rhabdovirus-based vectors as Hepatitis C vaccines. Virology, 2002, 292, 24-34.
  • Harty R.N., Brown M.E., McGettigan J.P., Wang G., Jayakar H.R., Huibregtse J.M., Whitt M.A., and Schnell M.J. Rhabdoviruses and cellular ubiquitin/proteasome system: a budding interaction? J. Virol., 2001, 75, 10623-10629.
  • McGettigan J.P., Sarma S., Orenstein J.M., Pomerantz R.J., and Schnell M.J. Expression and Immunogenicity of Human Immunodeficiency Virus Type I Gag Expressed by a Replication-competent Rhabdovirus-based Vaccine Vector. J. Virol, 2001, 75, 8724-8732.
  • McGettigan J.P., Foley H.D., Belyakov I.M., Berzofsky J.A., Pomerantz R.J., and Schnell, M.J. Rabies Virus-Based Vectors Expressing HIV-1 Envelope Protein Induce a Strong, Cross-Reactive Cytotoxic T-Lymphocyte Response Against Envelope Proteins from Different HIV-1 Isolates. J. Virol., 2001, 75, 4430-4434.
  • Morimoto K., Schnell M.J., Foley H.D., Pulmanausahakul R., McGettigan J.P., Hooper, D.C., and Dietzschold, B. High level expression of a human rabies virus-neutralizing monoclonal antibody by a rhabdovirus-based vector. J. Immunol. Methods, 2001, 252, 199-206.
  • Morimoto K., McGettigan J.P., Foley H.D., Hooper D.C., Dietzschold B., and Schnell M.J. Genetic engineering of live rabies vaccines. Vaccine, 19, 2001, 3543-3551.
  • Foley H.D, McGettigan J.P., Siler C.A., Dietzschold B., and Schnell, M.J. A Recombinant Rabies Virus Expressing Vesicular Stomatitis Virus Glycoprotein fails to protect against rabies virus infection. PNAS, 2000, 97, 14680-14685
  • Morimoto K., Foley H.D., McGettigan J.P., Schnell M.J., and Dietzschold, B. Reinvestigation of the role of the rabies virus glycoprotein in viral pathogenesis using a reverse genetics approach. J. of Neurovirology, 2000, 6, 373-381.
  • Schnell M.J., Foley H., Siler C.A., McGettigan J.P., Dietzschold B., and Pomerantz R.J. Recombinant rabies virus as potential live-viral vaccines for HIV-1, PNAS 2000, 97, 3544-3549.

Individual Expertise profile of James P McGettigan, PhD, Copyright © James P McGettigan, PhD.
Last Updated by James McGettigan, PhD : Monday, January 2, 2012 12:44:51 PM



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