Nancy Sullivan | |
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Born | Nancy Jean Sullivan |
Alma mater | Harvard T.H. Chan School of Public Health (ScD) |
Known for | Filovirus immunology, vaccine development |
Scientific career | |
Fields | Cell biology |
Institutions | Vaccine Research Center |
Thesis | Determinants of HIV-1 envelope glycoprotein-mediated fusion and antibody neutralization (1997) |
Doctoral advisor | Joseph Sodroski |
Nancy Jean Sullivan is an American cell biologist researching filovirus immunology and vaccine development. She is a senior investigator and chief of the biodefense research section at the Vaccine Research Center. Her team discovered the monoclonal antibody, mAb114.
Sullivan completed a doctor of science from Harvard T.H. Chan School of Public Health in 1997. She conducted a dissertation in the laboratory of Joseph Sodroski, where her work demonstrated that primary HIV isolates exhibit resistance to antibody neutralization due to occlusion of the coreceptor binding site on gp120. [1] [2] Following her work on HIV, Sullivan pursued postdoctoral training under the guidance of Gary Nabel, studying the mechanisms of Ebola virus pathogenesis and immune protection. [2]
Sullivan is a cell biologist. [3] She is a tenured senior investigator and chief of the biodefense research section at the Vaccine Research Center. [2]
Sullivan’s research is on the immunologic correlates and mechanisms of protection against infection by hemorrhagic fever viruses including Ebola virus. Her work on filovirus immunology and vaccine development is widely considered as one of the very best in the field despite the difficulties of conducting research under highly specialized BSL-4 containment conditions. Sullivan’s innovative and specialized work on filovirus immunology is recognized worldwide and has consistently been the source of novel observations that have contributed to critical advancements in the field. [2]
Sullivan’s long-term commitment to Ebola research has resulted in discovery of both vaccines and therapies. By using a novel gene-based prime boost vaccine, Sullivan and her team were the first to demonstrate vaccine protection against Ebola infection in primates. This was followed by her discovery of a single shot vaccine that provided more immediate protection, making it a very practical vaccine that could be used in the face of an acute Ebola epidemic. As a result, this vaccination schedule is now standard in the field of Ebola vaccine research, where one of the lead Ebola vaccine candidates, ChAd3-EBOV, has been advanced to Phase I/II and III human clinical trials. More recently, Sullivan and her team discovered a potently protective monoclonal antibody, mAb114, from a human Ebola survivor that completely rescues Ebola-infected primates, even when given as a monotherapy several days after their Ebola exposure. [2]
An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals.
Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.
In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.
Passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.
Antonio Lanzavecchia is an Italian and Swiss immunologist. As a fellow of Collegio Borromeo he obtained a degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases. He is Head Human Immunology Program, Istituto Nazionale di Genetica Molecolare-INGM, Milan and SVP Senior research Fellow, Humabs/Vir Biotechnology, Bellinzona and San Francisco (USA). Since 2017, he is also Professor at the Faculty of Biomedical Sciences of the Università della Svizzera italiana (USI).
Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication. The suboptimal antibodies can result from natural infection or from vaccination. ADE may cause enhanced respiratory disease, but is not limited to respiratory disease. It has been observed in HIV, RSV virus and Dengue virus and is monitored for in vaccine development.
The Vaccine Research Center (VRC), is an intramural division of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), US Department of Health and Human Services (HHS). The mission of the VRC is to discover and develop both vaccines and antibody-based products that target infectious diseases.
2F5 is a broadly neutralizing human monoclonal antibody (mAb) that has been shown to bind to and neutralize HIV-1 in vitro, making it a potential candidate for use in vaccine synthesis. 2F5 recognizes an epitope in the membrane-proximal external region (MPER) of HIV-1 gp41. 2F5 then binds to this epitope and its constant region interacts with the viral lipid membrane, which neutralizes the virus.
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, intracellular bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.
Barton Ford Haynes is an American physician and immunologist internationally recognized for work in T-cell immunology, retrovirology, and HIV vaccine development. Haynes is a Frederic M. Hanes Professor of Medicine and Immunology at Duke University Medical Center. He is the director of the Duke Human Vaccine Institute and the Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), which was funded by the National Institute of Allergy and Infectious Diseases (NIAID) in 2012. In addition, Haynes directs the B-cell Lineage Envelope Design Study, the Centralized Envelope Phase I Study, and the Role of IgA in HIV-1 Protection Study as part of the Collaboration for AIDS Vaccine Discovery (CAVD), which was funded by the Bill and Melinda Gates Foundation in 2006.
ZMapp is an experimental biopharmaceutical drug comprising three chimeric monoclonal antibodies under development as a treatment for Ebola virus disease. Two of the three components were originally developed at the Public Health Agency of Canada's National Microbiology Laboratory (NML), and the third at the U.S. Army Medical Research Institute of Infectious Diseases; the cocktail was optimized by Gary Kobinger, a research scientist at the NML and underwent further development under license by Mapp Biopharmaceutical. ZMapp was first used on humans during the Western African Ebola virus epidemic, having only been previously tested on animals and not yet subjected to a randomized controlled trial. The National Institutes of Health (NIH) ran a clinical trial starting in January 2015 with subjects from Sierra Leone, Guinea, and Liberia aiming to enroll 200 people, but the epidemic waned and the trial closed early, leaving it too statistically underpowered to give a meaningful result about whether ZMapp worked.
Julie E. Ledgerwood is an American allergist and immunologist, who is the chief medical officer and serves as chief of the Clinical Trials Program at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health in Bethesda, Maryland. She is a Doctor of Osteopathic Medicine.
Gary J. Nabel is an American virologist and immunologist, and President and chief executive officer of ModeX Therapeutics in Natick, Massachusetts.
Susan Zolla-Pazner is an American research scientist who is a Professor of Medicine in the Division of Infectious Diseases and the Department of Microbiology at Mount Sinai School of Medicine and a guest investigator in the Laboratory of Molecular Immunology at The Rockefeller University, both in New York City. Zolla-Pazner's work has focused on how the immune system responds to the human immunodeficiency virus (HIV) and, in particular, how antibodies against the viral envelope develop in the course of infection.
Ansuvimab, sold under the brand name Ebanga, is a monoclonal antibody medication for the treatment of Zaire ebolavirus (Ebolavirus) infection.
Nicole Amy Doria-Rose (born 1970) is an American biologist. She is chief of the humoral immunology core at the Vaccine Research Center. She develops and applies assays to evaluate HIV-1 specific antibody responses during natural infection and after immunization.
Catherine Blish is a translational immunologist and professor at Stanford University. Her lab works on clinical immunology and focuses primarily on the role of the innate immune system in fighting infectious diseases like HIV, dengue fever, and influenza. Her immune cell biology work characterizes the biology and action of Natural Killer (NK) cells and macrophages.
Atoltivimab/maftivimab/odesivimab, sold under the brand name Inmazeb, is a fixed-dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus. It contains atoltivimab, maftivimab, and odesivimab-ebgn and was developed by Regeneron Pharmaceuticals.
John R. Mascola is an American physician-scientist, immunologist and infectious disease specialist. He was the director of the Vaccine Research Center (VRC), part of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). He also served as a principal advisor to Anthony Fauci, director of NIAID, on vaccines and biomedical research affairs. Mascola is the current Chief Scientific Officer for ModeX Therapeutics.