Chief, Biodefense Research Section
Ebola and Marburg viruses have been identified as the cause of several highly lethal outbreaks of hemorrhagic fever for which there is no treatment or cure. Therefore, vaccine studies are critically important for protection against infection. The Biodefense Research Section (BRS) has developed highly effective vaccine strategies for Ebola virus infection in non-human primates. The vaccines are currently being tested in human trials conducted by the VRC Clinical Trials Core Laboratory in Bethesda, Maryland, and Makerere University in Uganda.
A second area of study is the analysis of vaccine-induced immune responses to better understand the mechanisms of immune protection against natural Ebola virus infection. We are using the nonhuman primate model for this study. Using multicolor flow cytometry, we are able to evaluate with high precision the quantity and quality of vaccine-induced cellular responses by identifying distinct subsets of lymphocytes that are present in protected animals and the kinetics with which they appear. We have shown that CD8+ cells are required for rAd Ebola vaccine protection and that the level of vaccine-induced antibodies correlates with protection but does not mediate protective responses when delivered by passive transfer. We are currently expanding these studies to define the relative or cooperative roles of antibodies and T lymphocytes for immune protection against Ebola.
Our laboratory is also interested the basic biology underlying Ebola virus pathogenesis, virus-host interactions, and inhibition of virus replication. Evaluation of immune responses in survivors of natural Ebola infection will help to elucidate immune mechanisms of protection, especially memory responses that are critical in a prophylactic vaccine. We have initiated a prospective study of more than 200 subjects in an Ebola-endemic region of West Africa to determine genetic and immunological factors mediating protection against Ebola infection. We have also obtained blood samples from individuals who survived the 1995 Ebola outbreak in Kikwit and are conducting a cross-sectional study to define antibody and T-lymphocyte responses associated with survival from infection. We identified durable antigen-specific T-cell responses in these subjects and also isolated and purified monoclonal antibodies from the B cells of these subjects. We are currently defining their critical characteristics for efficient clearance of virus by neutralization or antibody-dependent cytotoxicity. We have developed an array of antibodies, both neutralizing and non-neutralizing, that are useful for characterizing GP structural changes and their functional consequences. We are using these tools to dissect the molecular events underlying Ebola GP interactions within the host. Our goal with these studies is to identify points in the Ebola virus replication cycle that are vulnerable antiviral and neutralization targets.
Dr. Sullivan received her Ph.D. in cell biology/retrovirology from Harvard University in 1997. She received her master of science in environmental engineering in 1989, also from Harvard University. Dr. Sullivan was appointed as a tenure-track investigator and promoted to the position of chief, BRS, at the Vaccine Research Center in 2004.
Ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. Consequently, work with these viruses requires highly specialized BSL-4 containment. Dr. Sullivan is a leader in the field and has personally conducted many of the most critical experiments. Her work on filovirus immunology and vaccine development is widely considered as one of the very best in the filovirus field and, in spite of the difficulties associated with access to a BSL-4 laboratory, her work has consistently been the source of novel observations.
Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med. 2011 Aug 21;17(9):1128-31.
Geisbert TW, Bailey M, Geisbert JB, Asiedu C, Roederer M, Grazia-Pau M, Custers J, Jahrling P, Goudsmit J, Koup R, Sullivan NJ. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburg virus in nonhuman primates. J Virol. 2010 Oct;84(19):10386-94.
Hensley LE, Mulangu S, Asiedu C, Johnson J, Honko AN, Stanley D, Fabozzi G, Nichol ST, Ksiazek TG, Rollin PE, Wahl-Jensen V, Bailey M, Jahrling PB, Roederer M, Koup RA, Sullivan NJ. Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus species. PLoS Pathog. 2010 May 20;6(5):e1000904.
Chandran K, Sullivan NJ, Felbor U, Whelan SP, Cunningham JM. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science. 2005 Jun 10;308(5728):1643-5.
Sullivan NJ, Geisbert TW, Geisbert JB, Xu L, Yang ZY, Roederer M, Koup RA, Jahrling PB, Nabel GJ. Accelerated vaccination for Ebola virus haemorrhagic fever in nonhuman primates. Nature. 2003 Aug 7;424(6949):681-4.
Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature. 2000 Nov 30;408(6812):605-9.
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Last Updated February 10, 2015