Larner College of Medicine

Sean A Diehl

Professor, Microbiology & Molecular Genetics

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Alma mater(s)
  • Ph.D., Cell and Molecular Biology (Immunobiology), University of Vermont
  • B.S., Biology/Chemistry, State University of New York, Geneseo, NY
  • Fellowship, Human Immunology, (NIH NSRA F32 Fellow) University of Amsterdam
Affiliated Department(s)

Department of Microbiology and Molecular Genetics

College of Agriculture and Life Sciences

Vaccine Testing Center

Areas of expertise

immunology, viral infections, vaccines, T cells, B cells, adaptive immunity

BIO

Sean Diehl, PhD is a Professor of Microbiology and Molecular Genetics in the Larner College of Medicne and College of Agriculture and Life Sciences. He is also an investigator at the Vaccine Testing Center where he and his team research new immunological mechanisms that are engaged during viral infections and the vaccines designed to prevent the diseases they cause. His teaching in the undergraduate, graduate, and medical curricula are focused on the underpinnings and the endless applications of the immune system. He serves UVM as the Chair of the Institutional Biosafety Committee and as an active faculty member in the Graduate College.

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 in Immunology 
  • LCOM Foundations in Clinical Science 
  • LCOM Attacks and Defenses

Publications

PubMed Publications

Awards and Achievements

  • 2024 -2025 FDA and worldwide approval of Nirsevimab for infants (preventative antibody against respiratory synctial virus) 
  • 2024 UVM Emerging Research Leader 
  • 2023 University of Vermont President’s Faculty Colloquium 
  • 2021 Elected to Henry Kunkel Society (400 worldwide members) 
  • 2020 UVM 2020 Invention 2 Venture (I2V) License Award for-profit licensing of best-in-class anti-Zika virus antibodies 
  • 2016 Inducted into Rome, NY Science Hall of Fame 
  • 2012, 2015 NIH Clinical Research Loan Repayment Program Award 
  • 2005-2008 F32 Ruth Kirchstein National Service Award Postdoctoral Fellow, University of Amsterdam

Bio

Sean Diehl, PhD is a Professor of Microbiology and Molecular Genetics in the Larner College of Medicne and College of Agriculture and Life Sciences. He is also an investigator at the Vaccine Testing Center where he and his team research new immunological mechanisms that are engaged during viral infections and the vaccines designed to prevent the diseases they cause. His teaching in the undergraduate, graduate, and medical curricula are focused on the underpinnings and the endless applications of the immune system. He serves UVM as the Chair of the Institutional Biosafety Committee and as an active faculty member in the Graduate College.

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 in Immunology 
  • LCOM Foundations in Clinical Science 
  • LCOM Attacks and Defenses

Awards and Achievements

  • 2024 -2025 FDA and worldwide approval of Nirsevimab for infants (preventative antibody against respiratory synctial virus) 
  • 2024 UVM Emerging Research Leader 
  • 2023 University of Vermont President’s Faculty Colloquium 
  • 2021 Elected to Henry Kunkel Society (400 worldwide members) 
  • 2020 UVM 2020 Invention 2 Venture (I2V) License Award for-profit licensing of best-in-class anti-Zika virus antibodies 
  • 2016 Inducted into Rome, NY Science Hall of Fame 
  • 2012, 2015 NIH Clinical Research Loan Repayment Program Award 
  • 2005-2008 F32 Ruth Kirchstein National Service Award Postdoctoral Fellow, University of Amsterdam

Lab Team

Benjamin McElvany
Nancy Graham
Hector Granela
Gaby Madrigal

Select Publications

  • Gebo C, Hardy CSC, McElvany BD, Graham NR, Lu J, Moradpour S, Currier JR, Friberg H, Gromowski GR, Thomas SJ, Chan GC, Diehl SA, Waickman AT. B cell receptor dependent enhancement of dengue virus infection. (2024) PLoS Pathog. 20(10):e1012683. PMCID: PMC11556684 
  • Hanley J, Tu HA, Dragon J, Dickson DM, Selig N, Tighe S, Eckstrom K, Scarpino SV, Whitehead SS, Durbin AP, Pierce KK, Kirkpatrick BD , Rizzo DM, Frietze, S, and Diehl SA*. Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model. Nature Communications. (2021) May 24;12(1):3054. *corresponding author. PMCID: PMC8144425. Covered by Genetic Engineering and Biotechnology News. 
  • Tu HA, Nivarthi UK, Delacruz, MJ, Pierce, KK, Whitehead SS, Boyson JE, Botten JW, Kirkpatrick BD, Durbin AP, DeSilva AM, Diehl SA*. Stimulation of B cell immunity in flavivirus-naïve individuals by the tetravalent live attenuated dengue vaccine TV003. Cell Reports Medicine (2020) 1(9): 100155. PMCID: PMC7762770 
  • Graham NR, Whitaker AN, Strother CA, Miles AK, Grier D, McElvany BD, Bruce EA, Poynter ME, Pierce KK, Kirkpatrick BD, Stapleton RD, An G, Botten JW, Crothers JW, Diehl SA* Kinetics and isotype assessment of antibodies targeting the spike protein receptor-binding domain of severe acute respiratory syndrome-coronavirus-2 in COVID-19 patients as a function of age, biological sex and disease severity. Clin. Transl. Immunol. (2020) 9: e1189. 
  • Kwakkenbos MJ, Diehl SA*, Yasuda E, Bakker AQ, van Geelen CM, Lukens MV, van Bleek GM, Widjojoatmodjo MN, Bogers WM, Mei H, Radbruch A, Scheeren FA, Spits H, Beaumont T. Generation of stable monoclonal antibody-producing B cell receptor-positive human memory B cells by genetic programming. Nat Med. 2010;16(1):123-8. PMCID: PMC2861345.