Faculty

Simon M. Barratt-Boyes, BVSc, PhD Associate Professor, Department of Infectious Diseases and Microbiology and Department of Immunology, School of Medicine (Secondary Appointment) E-mail: smbb@pitt.edu Phone: 412-383-7537 Address: Center for Vaccine Research 9046 BST3 3501 Fifth Avenue Pittsburgh, PA  15260

Education

BVSc; Massey University, New Zealand; 1984
PhD; University of California, Davis; 1993

Research Interests

Dendritic cell biology and therapy; primate models of infectious disease

Research Summary

	Figure caption: Dendritic cells expressing green fluorescent protein via recombinant adenovirus transduction are localized in the T cell-rich region of the lymph node after injection in a monkey
	Figure caption:Human dendritic cells stained with antibodies to CD11c (blue) and early endosomal antigen (red). Image courtesy of S. Gleason

Our research focuses on the immunology of infectious diseases, with the ultimate goal of exploiting the immune system for improved vaccination and disease control. A lot of our work focuses on dendritic cells (DC), which are critical in the initiation of immune responses to pathogens. The animal model we primarily study is the simian model of human immunodeficiency virus infection, being simian immunodeficiency virus or SIV, although we do basic immunology work using human cells. There are three major lines of investigation currently ongoing in the lab.

Dendritic cell biology in healthy and SIV-infected rhesus macaques: Studies in the human show that the two main subsets of DC, myeloid DC and plasmacytoid DC, are lost from the circulation in individuals with HIV infection associated with progression to disease. We have characterized DC subsets in blood and lymphoid tissues of healthy rhesus macaques and macaques with SIV infection. We have found that mDC and pDC are lost from blood in monkeys with AIDS, as in humans with HIV infection, and are also depleted from lymph nodes and spleen in these animals. This suggests that DC are not recruited to lymphoid tissues in progressive disease but rather undergo a systemic depletion. We are currently investigating the mechanism of this loss. We are also moving into the acute infection model and will evaluate DC dynamics in monkeys with acute SIV infection.

Dendritic cell- and vector-based immunotherapy: There is a lot of interest in using DC as antigen-presenting cells to deliver viral or tumor-associated antigens to T cells in immunotherapy. We have developed an mRNA approach to transfect monkey and human DC with viral antigens and have demonstrated that nucleofection with mRNA is a superior method for introducing transgenes into primary DC lines and for subsequent stimulation of virus-specific T cells. Adenoviral vectors are also potent vehicles for transducing DC and have been used to great effect as vaccines when given directly to monkeys or human volunteers. We have used recombinant adenoviral vectors as vaccines for SIV infection and for highly pathogenic avian influenza virus infection. Currently we are using adenovirus-5 and 35-based vectors in combination as an immunotherapy for monkeys that are infected with SIV and treated with antiretroviral drugs to control virus load.

Dendritic cell capture of cell-associated antigens
We have studied the interaction of DC with other cells and have shown that DC capture antigens from living cells and cross-present peptides from these antigens to cytotoxic T cells, a process known as ‘nibbling’. Work in the lab is currently looking at how the different sources of cellular antigens – from live cells or apoptotic cells – affects the process and efficiency of antigen capture. These studies involve confocal and live-cell imaging assays in collaboration with the Center for Biologic Imaging.

Recent Publications

• Harshyne, L.A., Zimmer, M.I., Watkins, S.C. and Barratt-Boyes, S.M. (2003). A role for class A scavenger receptor in dendritic cell nibbling from live cells. Journal of Immunology, 170: 2302-2309.
• Brown, K., Gao, W., Alber, S., Trichel, A., Murphey-Corb, M., Watkins, S.C., Gambotto, A. and Barratt-Boyes, S.M. (2003). Adenovirus-transduced dendritic cells injected into skin or lymph node prime potent SIV-specific T-cell immunity in monkeys. Journal of Immunology, 171: 6875-6882.
• Gao, W., Tamin, A., Soloff, A., D'Aiuto, L., Nwanegbo, E., Robbins, P.D., Belini, W.J., Barratt-Boyes, S.M. and Gambotto, A. (2003). Effects of a SARS-associated coronvirus vaccine in monkeys. The Lancet, 362: 1895-1896.
• Barratt-Boyes, S.M. and Figdor, C.G. (2004). Current issues in delivering DCs for immunotherapy. Cytotherapy, 6: 105-110.
• Barratt-Boyes, S.M. and Thomson, A.W. (2005). Dendritic cells: Tools and targets for transplant tolerance. American Journal of Transplantation, 5:2807-2813.
• Barratt-Boyes, S.M., Soloff, A.C., Gao, W., Nwanegbo, E., Liu, X., Rajakumar, P.A., Brown, K.N., Robbins, P.D., Murphey-Corb, M., Day, R.D. and Gambotto, A. (2006). Broad cellular immunity with robust memory responses to simian immunodeficiency virus following serial vaccination with adenovirus 5- and 35-based vectors. Journal of General Virology, 87: 139-149.
• Gao, W., Soloff, A.C., Lu, X., Montecalvo, A., Nguyen, D.C., Matsuoka, Y., Robbins, P.D., ­Swayne, D.E., Donis, R.O., Katz, J.M., Barratt-Boyes, S.M., and Gambotto, A. (2006). Protection in mice and poultry from lethal H5N1 avian influenza through adenovirus-based immunization. Journal of Virology, 80: 1959-1964.
• Brown, K.N., Trichel, A. & Barratt-Boyes, S.M. (2007) Parallel loss of myeloid and plasmacytoid dendritic cells from blood and lymphoid tissues in simian AIDS. Journal of Immunology,178: 6958-6967.
• Melhem. N.M., Liu, X.D., Boczowski, D., Gilboa, E. & Barratt-Boyes, S.M. (2007) Robust CD4+ and CD8+ T cell responses to SIV using mRNA-transfected dendritic cells expressing autologous viral antigen.  European Journal of  Immunology,37: 2164-2173.

Dr. Barratt-Boyes' Lab

L-R: Nicole Banichar, Adam Soloff, Nada Melhem (graduated September 2007), Sherrianne Gleason, Kevin Brown, Xiangdong Liu, Viskam Wijewardana

Staff

Nicole Banichar, Veterinary Technician (Research III)
Primate Facility for Infectious Disease Research; nib12@pitt.edu

Xiang Dong Liu, Research Specialist III
BST3, 9th floor, Room 9053; 412-383-9057; xil37@pitt.edu

Post Doctoral Fellow

Viskam Wijewardana, BVSc, PhD
BST3, 9th floor, Room 9053; 412-383-9057; viskam@cvr.pitt.edu

Students

Kevin Brown; Graduate Student Researcher
BST3, 9th floor, Room 9053; 412-383-9057; knbidm@pitt.edu

Sherrianne Gleason; Graduate Student Researcher
BST3, 9th floor, Room 9053; 412-383-9057; smg55@pitt.edu

Adam Soloff; Graduate Student Researcher
BST3, 9th floor, Room 9053; 412-383-9057; adamsoloff@hotmail.com