Sean A Diehl, PhD
Associate Professor
Human Immune Responses to Infection and Vaccination
sean.diehl@med.uvm.edu
Stafford Hall 224B
95 Carrigan Drive
Burlington, VT 05405
United States
Alma mater(s)
- University of Vermont
Affiliated Department(s)
Dept of Microbiology and Molecular Genetics
Area(s) of expertise
- Human Immunology and viral vaccines
- Viral infections: dengue virus, zika viurs, norovirus, sapovirus
- B cells and monoclonal antibody isolation and uses
- T cell responses to dengue virus
The immune system protects us from infectious agents, but when functioning improperly, can also cause disease. My research is aimed at determining the molecular mechanisms occurring in immune cells that control these responses. We study the cellular response to infection, but also seek to understand about the intracellular response of immune cells in the context of inflammatory diseases such as allergic asthma. To address these questions, our lab utilizes in vitro culture of primary human cells, flow cytometry, mRNA analysis, immunostaining, as well as stable in vitro genetic modification of primary human lymphocytes derived from both control and patient populations.
BIO
- Education and Training
- 1998, B.S., Biology, State University of New York at Geneseo, NY
- 2003, Ph.D., Cell and Molecular Biology, University of Vermont. Mentor: Mercedes Rincon, Ph.D.
- 2008, Postdoctoral fellowship in human Immunology (NIH NSRA F32 fellow), University of Amsterdam. Mentor: Hergen Spits, Ph.D.
- Research summary
- Our research program focuses on understanding how human B and T cells “store” information on previous infectious threats, primarily RNA viruses including dengue virus, zika virus, norovirus, and sapovirus. The development of immune memory is central to resistance to severe disease following re-exposure and to vaccine development. Our goal is to define products and characteristics of protective immune responses following viral exposure to uncover basic mechanisms of how B cells and their antibody products alongside T cells block viral pathogenesis. This work provides insight into the generation of immune memory to support vaccine development. Our work is highly collaborative with other investigators and clinician scientists at UVM, other top universities across the U.S., and in low-to-middle income countries including Bangladesh and Guatemala.
- Highlights:
- In collaboration with the Vaccine Testing Center, Johns Hopkins University, and NIH, we have been studying immune responses underlying how a live attenuated dengue vaccine protects against infection with serotypes 2 and 3 in controlled trials in the U.S. and in Bangladesh.
- Development of an approach to immortalize memory B cells from humans to isolate potent monoclonal antibodies that can be used as prophylactics, diagnostics, and tools to study virus biology.
- FDA approval and roll-out of Beyfortus (Nirsevimab), a monoclonal antibody to prevent respiratory syncytial virus (RSV) disease in infants as part of the CDC’s free Vaccines for Children immunization program. *Our immortalization approach yielded D25, the precursor antibody to Nirsevimab.
- Isolation of three ultra-potent monoclonal antibodies against Zika virus from recovered individuals. Mechanisms of virus neutralization studied collaboratively with teams at U. North Carolina, and in Singapore.
- Characterization of the first infant-derived human monoclonal antibody to the GII.17 genotype of norovirus, one of the top 4 disease-causing genotypes in infants.
- Investigations into both systemic immune gene expression changes and localized tissue responses to infection with dengue virus.
Courses
- MMG 3230 Immunology
- MMG 5230 Immunology Concepts
Bio
- Education and Training
- 1998, B.S., Biology, State University of New York at Geneseo, NY
- 2003, Ph.D., Cell and Molecular Biology, University of Vermont. Mentor: Mercedes Rincon, Ph.D.
- 2008, Postdoctoral fellowship in human Immunology (NIH NSRA F32 fellow), University of Amsterdam. Mentor: Hergen Spits, Ph.D.
- Research summary
- Our research program focuses on understanding how human B and T cells “store” information on previous infectious threats, primarily RNA viruses including dengue virus, zika virus, norovirus, and sapovirus. The development of immune memory is central to resistance to severe disease following re-exposure and to vaccine development. Our goal is to define products and characteristics of protective immune responses following viral exposure to uncover basic mechanisms of how B cells and their antibody products alongside T cells block viral pathogenesis. This work provides insight into the generation of immune memory to support vaccine development. Our work is highly collaborative with other investigators and clinician scientists at UVM, other top universities across the U.S., and in low-to-middle income countries including Bangladesh and Guatemala.
- Highlights:
- In collaboration with the Vaccine Testing Center, Johns Hopkins University, and NIH, we have been studying immune responses underlying how a live attenuated dengue vaccine protects against infection with serotypes 2 and 3 in controlled trials in the U.S. and in Bangladesh.
- Development of an approach to immortalize memory B cells from humans to isolate potent monoclonal antibodies that can be used as prophylactics, diagnostics, and tools to study virus biology.
- FDA approval and roll-out of Beyfortus (Nirsevimab), a monoclonal antibody to prevent respiratory syncytial virus (RSV) disease in infants as part of the CDC’s free Vaccines for Children immunization program. *Our immortalization approach yielded D25, the precursor antibody to Nirsevimab.
- Isolation of three ultra-potent monoclonal antibodies against Zika virus from recovered individuals. Mechanisms of virus neutralization studied collaboratively with teams at U. North Carolina, and in Singapore.
- Characterization of the first infant-derived human monoclonal antibody to the GII.17 genotype of norovirus, one of the top 4 disease-causing genotypes in infants.
- Investigations into both systemic immune gene expression changes and localized tissue responses to infection with dengue virus.
Courses
- MMG 3230 Immunology
- MMG 5230 Immunology Concepts
Lab Team
Benjamin McElvany
Nancy Graham
Hector Granela
Gaby Madrigal
Emma Steenbergen
Nancy Graham
Hector Granela
Gaby Madrigal
Emma Steenbergen