Faculty

Kelly Stefano Cole, PhD Associate Director of RBL, Center for Vaccine Research, Assistant Professor of Immunology and Department of Infectious Diseases and Microbiology - Graduate School of Public Health (Secondary Appointment) E-mail: stefcole@cvr.pitt.edu Phone: 412-648-8583 Fax: 412-648-8521 Address: 8039 BST3 3501 Fifth Avenue Pittsburgh, PA 15260

Education

BS; Mt. St. Mary’s College, 1987
PhD; University of Pittsburgh, 1994

Research Interests

Characterizing protective antibody responses to SIV and HIV infection and vaccination; defining mechanisms and identifying the role of variation on antibody-mediated neutralization; antigen-antibody interactions; B cell responses to chronic virus infections.

Research Summary

Our research focuses on understanding the role of humoral immune responses involved in HIV-1 and the closely related SIV infection and vaccination. We are interested in defining the mechanisms involved in antibody-mediated virus neutralization in vitro, evaluating the effects of variation on virus neutralization in vitro and in vivo, and determining the role of neutralizing antibody in the control of infection and disease progression in vivo. For these studies, we have recently focused our efforts on the real-time binding of virus-specific antibody to envelope antigens using biosensor analyses, and recently have turned to defining the specific envelope determinants involved in antibody binding. Ultimately, our goal is to apply similar neutralization studies of HIV-1 to vaccinated and infected patients . A second major goal of the lab is to characterize the protective immune responses to experimental infection and vaccination in the SIV/monkey model system as a basis for the development and evaluation of effective AIDS vaccines. We are interested in the development of novel assays to characterize the maturation of antibody responses to SIV and HIV-1 envelope proteins, the evaluation of antibody responses elicited by diverse vaccine strategies as correlates of protection, and the application of biochemical and molecular approaches to identify functional and antigenic determinants of these envelope proteins. We are currently focusing our efforts on characterizing the maturation of B cell responses to chronic virus infection, and to studies involving characterization of the immunogenic and protective immune responses elicited by modified HIV-1 envelope vaccines using a DNA prime, virus-like particle boost regimen in both small animal and nonhuman primate models. For more information, the Cole Laboratory website can be accessed at http://www. pitt.edu/~disease/labs/labs.html#colelab.

Recent Publications

• Gupta S, Leutenegger CM, Dean GA, Steckbeck JD, Cole KS, Sparger EE.  Vaccination of cats with attenuated feline immunodeficiency virus proviral DNA vaccine expressing gamma interferon. J Virol 2007; 81:465-473.
• Milush JM, Reeves JD, Gordon SN, Zhou D, Muthukumar A, Kosub DA, Chacko E, Glavedoni LD, Ibegbu CC, Cole KS, Miamidian JL, Paiardini M, Barry AP, Staprans SI, Silvestri G, Sodora DL. Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host. J Immunol 2007; 179:3047-3056.
• Cole KS , Landucci G., Grieser HJ, Steckbeck JD, Forthal DN. Rhesus monoclonal antibodies identify epitopes in SIV gp120 that mediate antibody-dependent cell-mediated virus inhibition independent of virus neutralization. J Virol 2006; (Submitted).
  
• Milush JM, Reeves J, Zhou D, Muthukumar A, Chacko E, Paiardini M, Gordon S, Cole KS, Giavedoni L, Barry AP, Staprans S, Silvestri G, Sodora DL. Multi-tropic SIVsm and AIDS defining CD4 T cell levels in sooty mangabeys. J Exp Med 2006; (In Press).
  
• Steckbeck JD and Cole KS. Dissecting the humoral immune response to simian immunodeficiency virus: mechanisms of antibody-mediated virus neutralization. Imm Res 2006; 36:51-60.
  
• McBurney SP, Young KR, Nwaigwe CI, Soloff AC, Cole KS, Ross TM. Lentivirus-like particles without reverse transcriptase elicit efficient immune responses. Curr HIV Res 2006; 4:475-484.
  
• Steckbeck JD, Grieser HJ, Sturgeon TJ, Taber R, Chow A, Bruno J, Murphey-Corb M, Montelaro RC, Cole, KS. Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodefiency virus identified by surface plasmon resonance. J Med Primatol 2006; 35:248-260.
  
• Forthal DN, Landucci G, Cole KS, Becerra JC, Marthas M, Van Rompay K. Rhesus macaque polyclonal and monoclonal antibodies inhibit simian immunodeficiency virus (SIV) in the presence of human or autologous rhesus effector cells. J Virol 2006; J. Virol. 2006; 80:9217-9225.
  
• Steckbeck JD, Orlov I, Miller K, Chow A, Bruno J, Grieser HJ, Robinson JE, Montelaro RC, Cole KS. Kinetic rates of antibody binding correlate with neutralization sensitivity to simian immunodeficiency virus. J Virol. 2005; 79:12311-12320.
  
• Cole KS , Steckbeck JD, Rowles JL, Czajak SC, Desrosiers RC, Montelaro RC. Removal of N-linked glycosylation sites in the V1 region of SIV gp120 results in redirection of B-cell responses to V3. J Virol 2004, 78:1525-1539.
  
• Cole KS , Alvarez M, Elliott DH, Lam H, Rowles JL, Clements JE, Murphey-Corb M, Montelaro RC, Robinson JE. Rhesus monoclonal antibodies to simian immunodeficiency virus define nine binding domains on the surface envelope glycoprotein. Virology 200 1; 290:59-73.
  
• Cole KS , Paliotti MJ, Robinson JE, Montelaro RC. Maturation of envelope-specific antibody responses to linear determinants in monkeys inoculated with attenuated SIV. J Med Primatol 2000; 29:220-230
  
• Montelaro RC, Cole KS Hammond SA. Maturation of immune responses to lentivirus infection: implications for AIDS vaccine development. AIDS Res Hum Retro 1998; 14:S255-S259.
  
• Robinson JE, Cole KS, Elliott DH, Lam H, Amedee AM, Means R, Desrosiers RC, Clements JE, Montelaro RC Murphey-Corb M. Production and characterization of SIV envelope-specific rhesus monoclonal antibodies from a macaque asymptomatically infected with a live SIV vaccine. AIDS Res Hum Retro1998; 14:1253-1262.
  
• Cole KS , Murphey-Corb M, Narayan O, Joag SV, Shaw GM Montelaro RC. Common themes of antibody maturation in SIV, SHIV and HIV-1 infections. J Virol1998; 10:7852-7859.
  
• Cole KS , Rowles JL, Murphey-Corb M, Clements JE, Unangst T, Robinson J, Desrosiers RC, Wyand MS, Montelaro RC. Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with SIV and its association with the development of protective immunity. J. Virol 1997; 71:5069-5079.

 

Last Updated: January 23, 2008