Arbovirus Immunity Section
Theodore C. Pierson, Ph.D.
Chief, Arbovirus Immunity Section
Director, Vaccine Research Center
Acting Chief, Humoral Immunology Section
Contact: piersontc@mail.nih.gov
Major Areas of Research
- Flavivirus assembly and entry
- Humoral immunity to arbovirus infections
- Arbovirus vaccine design and evaluation
Program Description
Flaviviruses are small RNA viruses responsible for considerable morbidity and mortality worldwide. Flaviviruses are endemic to and cause disease in many regions that support their arthropod vectors. Each year, dengue virus (DENV) alone results in an estimated 390 million infections. Flaviviruses have considerable potential for emergence and explosive transmission, as observed with West Nile virus (WNV) and Zika virus (ZIKV) in the Americas during the past twenty-five years. The re-emergence of yellow fever virus (YFV) is also alarming. Fortunately, vaccines have proven effective at controlling flaviviruses. Human vaccines are available for YFV, Japanese encephalitis virus, tickborne encephalitis virus, and DENV. Neutralizing antibodies (Nabs), which bind to the surface of the virus to directly inhibit infectivity, are a surrogate of vaccine-elicited protection for many flaviviruses. Complicating an understanding of humoral immunity to flaviviruses is the potential for virus-reactive antibodies to augment infection of Fc receptor-expressing cells. This mechanism is called antibody-dependent enhancement of infection (ADE) and has been linked mechanistically to severe DENV disease. Understanding of the role of Nabs in protection from infection and how to measure protective responses in clinical trials is critical. A goal of the Arbovirus Immunity Section (AIS) is to understand the mechanisms of action of anti-flavivirus antibodies, the complexity of antibody responses elicited by flavivirus infection or vaccination, and the antigenic features of protective vaccine antigens.
Biography
Education
Ph.D., 2001, The Johns Hopkins University School of Medicine, Baltimore, MD
Dr. Ted Pierson is the Director of the VRC. As Director, he leads the VRC’s comprehensive basic, translational, and clinical research programs focused on designing, developing, and testing candidate vaccines and biologics against HIV/AIDS, coronaviruses, influenza, and emerging infectious diseases with pandemic potential. Dr. Pierson also serves as Chief of the VRC’s Arbovirus Immunity Section. His research explores fundamental and translational questions related to arbovirus assembly and entry, humoral immunity, and vaccine design and evaluation.
Dr. Pierson received a B.S. in marine science from Eckerd College and a Ph.D. in immunology from the Johns Hopkins University School of Medicine. During his graduate studies with Dr. Robert F. Siliciano, he investigated the molecular biology of the pre-integration state of HIV-1 latency and the contribution of this reservoir toward the persistence of HIV-1 in humans. Dr. Pierson trained as a postdoctoral fellow and research associate with Dr. Robert W. Doms at the University of Pennsylvania, where he developed an interest in the virology and immunology of arboviruses, including West Nile and dengue viruses. In 2005, Dr. Pierson was recruited to the NIAID Division of Intramural Research program’s Laboratory of Viral Diseases (LVD) to initiate an independent research program focused on flavivirus biology, and in 2011, became a tenured Senior Investigator and Chief of the Viral Pathogenesis Section. He was named Chief of the LVD in 2018 and served in that role until he was appointed VRC Director in 2023.
Dr. Pierson served as the Deputy Scientific Director and later Scientific Director of the NIH Oxford Cambridge Scholars Program between 2014-2018. He has co-authored more than 130 publications and has served on the editorial boards of several scientific journals and as an editor for PLoS Pathogens and the Journal of Virology. Dr. Pierson is an American Academy of Microbiology Fellow and recipient of the NIH Director’s Ruth L. Kirschstein Mentoring Award.
Selected Publications
Maciejewski S, Ruckwardt TJ, Morabito KM, Foreman BM, Burgomaster KE, Gordon DN, Pelc R, DeMaso CR, Ko SY, Fisher BE, Yang ES, Nair D, Foulds KE, Todd JP, Kong WP, Roy V, Aleshnick M, Speer SD, Bourne N, Barrett AD, Nason MC, Roederer M, Gaudinski MR, Chen GL, Dowd KA, Ledgerwood JE, Alter G, Mascola JR, Graham BS, Pierson TC. Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality. Sci Transl Med. 2020;12(547):eaaw9066.
Dowd KA, Ko SY, Morabito KM, Yang ES, Pelc RS, DeMaso CR, Castilho LR, Abbink P, Boyd M, Nityanandam R, Gordon DN, Gallagher JR, Chen X, Todd JP, Tsybovsky Y, Harris A, Huang YS, Higgs S, Vanlandingham DL, Andersen H, Lewis MG, De La Barrera R, Eckels KH, Jarman RG, Nason MC, Barouch DH, Roederer M, Kong WP, Mascola JR, Pierson TC, Graham BS. Rapid development of a DNA vaccine for Zika virus. Science. 2016;354(6309):237-40.
VanBlargan LA, Mukherjee S, Dowd KA, Durbin AP, Whitehead SS, Pierson TC. The type-specific neutralizing antibody response elicited by a dengue vaccine candidate is focused on two amino acids of the envelope protein.PLoS Pathog. 2013;9(12):e1003761.
Dowd KA, Jost CA, Durbin AP, Whitehead SS, Pierson TC. A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog. 2011;7(6):e1002111.
Nelson S, Jost CA, Xu Q, Ess J, Martin JE, Oliphant T, Whitehead SS, Durbin AP, Graham BS, Diamond MS, Pierson TC. Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization. PLoS Pathog. 2008;4(5):e1000060.
Pierson TC, Xu Q, Nelson S, Oliphant T, Nybakken GE, Fremont DH, Diamond MS. The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe. 2007;1(2):135-45.