Robert Alan Seder, M.D.

Senior Investigator

Cellular Immunology Section

NIAID/VRC

Building 40, Room 3512
40 Convent Drive
Bethesda, MD 20892

301-594-8483

rseder@nih.gov

Research Topics

The aim of the Cellular Immunology Section (CIS) is to provide a mechanistic basis for developing preventive vaccines against HIV, malaria, tuberculosis, SARS-CoV2 and therapeutic vaccines against cancer. More recently, there is a major focus on developing monoclonal antibodies against proteins expressed on malaria parasites to be used as passive prevention.

T cell Immunity: Based on the critical role of CD4 and CD8 T cells in mediating protection against infections and tumors, a major area of investigation is to understand how various vaccine platforms influence the magnitude, quality, breadth and tissue distribution following immunization. T-cell responses are assessed with a variety of technologies including advanced 30-color multi-parameter flow cytometry, single cell analysis by RNAseq, spatial transcriptomics and confocal imaging.

Innate Immunity: The laboratory has a major focus on determining how different immune adjuvants, formulation and delivery influence humoral and cellular immunity when administered with protein or peptide antigens specific for viral infections or cancer antigens. Recent work has focused on using polymer chemistry and other bio-engineering approaches with specific toll-like receptor (TLR) ligands (eg. TLR 7/8) or STING to tumor specific neo-antigen responses to be used for personalized cancer vaccines.

Vaccines: The laboratory has focused on vaccines against HIV, TB, malaria, cancer and more recently SARS-CoV2. These studies focus on using different vaccine formulations such as protein/adjuvant, viral vectors or synthetic nanoparticle vaccines alone or in heterologous prime boost combinations. There is a major emphasis on how the route of immunization influences antibody and T cell responses in tissues such as lung and liver which are important for mediating protection against respiratory infection or malaria respectively.

Malaria Monoclonal Antibodies: The laboratory has isolated a large number of human monoclonal antibodies against the major circumsporozoite surface protein expressed on P. falciparum sporozoites (PfCSP). The specificity and function of such antibodies binding to PfCSP are elucidated by epitope mapping, avidity and stoichiometry measurements and defining the crystal structure. in vivo imaging is used to understand the mechanism of how the antibodies mediate protection in the skin and liver.

Clinical Translation: 1) Malaria-Based on the discovery that intravenous immunization with an attenuated sporozoite vaccine induced a high frequency of tissue resident T cells in the liver in pre-clinical animal models, Dr. Seder has led several clinical trials in the US and Africa with an attenuated sporozoite vaccine given by the intravenous route for safety and clinical efficacy. In addition, Dr. Seder has recently performed the first in human clinical trial showing that a monoclonal antibody can prevent malaria infection in humans. This has led to several ongoing and planned trials to use monoclonal antibodies to prevent malaria infection in infants and children in Africa. 2) Personalized tumor vaccine- Based on the discovery/development of a personalized neoantigen peptide/adjuvant nanoparticle vaccine in pre-clinical models, there are plans for assessing this in human clinical trials.

Biography

Dr. Seder received his B.A. in Natural Science at Johns Hopkins University in 1981 and his M.D. at Tufts University in 1986 and completed his residency in internal medicine at New York Hospital-Cornell Medical Center. Dr. Seder did his postdoctoral training at NIAID with Dr. William Paul studying how cytokines influence CD4+ T helper cell differentiation.

In 1994, Dr. Seder became Chief of the Clinical Immunology Section in the Laboratory of Clinical Investigation, part of the NIAID Division of Intramural Research. Dr. Seder was then appointed to a tenured position in the Vaccine Research Center (VRC), Laboratory of Immunology in 2000. Since joining the VRC, Dr. Seder has focused his efforts on understanding the innate and adaptive mechanisms by which various vaccines approaches mediate protective antibody and T cell immunity in mouse, non-human primate and human models of HIV, Malaria and Tuberculosis infection. Dr. Seder is internationally recognized in the field of vaccine biology and cellular immunology. He currently serves as chief of the Cellular Immunology Section in the VRC.

Selected Publications

  1. Epstein JE, Tewari K, Lyke KE, Sim BK, Billingsley PF, Laurens MB, Gunasekera A, Chakravarty S, James ER, Sedegah M, Richman A, Velmurugan S, Reyes S, Li M, Tucker K, Ahumada A, Ruben AJ, Li T, Stafford R, Eappen AG, Tamminga C, Bennett JW, Ockenhouse CF, Murphy JR, Komisar J, Thomas N, Loyevsky M, Birkett A, Plowe CV, Loucq C, Edelman R, Richie TL, Seder RA, Hoffman SL. Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity. Science. 2011;334(6055):475-80.

  2. Ishizuka AS, Lyke KE, DeZure A, Berry AA, Richie TL, Mendoza FH, Enama ME, Gordon IJ, Chang LJ, Sarwar UN, Zephir KL, Holman LA, James ER, Billingsley PF, Gunasekera A, Chakravarty S, Manoj A, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, K C N, Murshedkar T, DeCederfelt H, Plummer SH, Hendel CS, Novik L, Costner PJ, Saunders JG, Laurens MB, Plowe CV, Flynn B, Whalen WR, Todd JP, Noor J, Rao S, Sierra-Davidson K, Lynn GM, Epstein JE, Kemp MA, Fahle GA, Mikolajczak SA, Fishbaugher M, Sack BK, Kappe SH, Davidson SA, Garver LS, Björkström NK, Nason MC, Graham BS, Roederer M, Sim BK, Hoffman SL, Ledgerwood JE, Seder RA. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nat Med. 2016;22(6):614-23.

  3. Seder RA, Chang LJ, Enama ME, Zephir KL, Sarwar UN, Gordon IJ, Holman LA, James ER, Billingsley PF, Gunasekera A, Richman A, Chakravarty S, Manoj A, Velmurugan S, Li M, Ruben AJ, Li T, Eappen AG, Stafford RE, Plummer SH, Hendel CS, Novik L, Costner PJ, Mendoza FH, Saunders JG, Nason MC, Richardson JH, Murphy J, Davidson SA, Richie TL, Sedegah M, Sutamihardja A, Fahle GA, Lyke KE, Laurens MB, Roederer M, Tewari K, Epstein JE, Sim BK, Ledgerwood JE, Graham BS, Hoffman SL, VRC 312 Study Team.. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 2013;341(6152):1359-65.

  4. Darrah PA, Patel DT, De Luca PM, Lindsay RW, Davey DF, Flynn BJ, Hoff ST, Andersen P, Reed SG, Morris SL, Roederer M, Seder RA. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med. 2007;13(7):843-50.

  5. Kisalu NK, Idris AH, Weidle C, Flores-Garcia Y, Flynn BJ, Sack BK, Murphy S, Schön A, Freire E, Francica JR, Miller AB, Gregory J, March S, Liao HX, Haynes BF, Wiehe K, Trama AM, Saunders KO, Gladden MA, Monroe A, Bonsignori M, Kanekiyo M, Wheatley AK, McDermott AB, Farney SK, Chuang GY, Zhang B, Kc N, Chakravarty S, Kwong PD, Sinnis P, Bhatia SN, Kappe SHI, Sim BKL, Hoffman SL, Zavala F, Pancera M, Seder RA. A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite. Nat Med. 2018;24(4):408-416.


This page was last updated on February 1st, 2022