Robert Seder, M.D.Vaccine Research CenterBuilding 40, Room 350440 Convent DriveBethesda, MD 20892-3025Phone (Office): 301-594-8483Phone (Lab): 301-594-8589Fax: email@example.com
Chief, Cellular Immunology Section
The aim of the Cellular Immunology Section (CIS) is to rationally design vaccines for diseases that require humoral and cellular immunity in humans such as HIV, malaria, and tuberculosis. One area of study is to define T-cell immune correlates of protection following vaccination. This involves using a variety of vaccine platforms (recombinant viral, protein/adjuvant, and attenuated whole organism vaccines to elicit T-cell immunity that confers protection. T-cell responses are assayed by multi-parameter flow cytometry, fluidigm, RNAseq, expression profiling, and assessment of breadth by epitope mapping in a variety of models including rodent, non-human primate, and human clinical studies.
In order to understand the cellular and molecular mechanisms by which viral vaccines and immune adjuvants induce adaptive immunity in vivo, we study the tropism of the vaccines or adjuvants for specific dendritic cell subsets and the breadth of innate immunity that is induced. The vaccines used in the study include recombinant replication defective adenovirus and poxvirus vaccines, as well as multiple toll-like receptor ligands given with proteins or antibodies targeted to specific dendritic cell subsets. We analyze how vaccine formulation and the type of toll-like receptor ligand influence the type of antibody and T-cell response. An analysis of CD4+ T cells is done to determine whether adjuvants alter the frequency of Th1, Th2, Th17 or T follicular helper cells. In addition, we also compare the immune responses from protein vaccines specifically targeted to surface receptors expressed on dendritic cells to non-targeted proteins. Recent work has used mice and nonhuman primates to understand how immune adjuvants alter the magnitude and quality of HIV Env specific B-cell immunity using 454 deep sequencing to assess somatic mutation. This work helps to design novel protein/adjuvant platforms for inducing potent humoral and cellular immune responses.
To apply the knowledge learned from the areas highlighted above, we use experimental mouse and nonhuman primate infection models of Leishmania major, Mycobacterium tuberculosis, Listeria monocytogenes, malaria, and HIV/SIV infection. Recent work has extended the assessment of a malaria vaccine to humans.
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 he completed his residency in internal medicine at New York Hospital-Cornell Medical Center. During his postdoctoral training at NIAID, Dr. Seder showed that cytokines such as IL-12 are critical for inducing Th1 responses, is the basis for design of vaccines in which such responses are important, such as HIV, malaria, and tuberculosis.
In 1994, Dr. Seder became a tenure-track investigator in the Laboratory of Clinical Investigation at NIAID. Dr. Seder was appointed to a tenured position in the VRC Laboratory of Immunology in 2000. His previous position was as chief of the Clinical Immunology Section in the Laboratory of Clinical Investigation, part of the NIAID Division of Intramural Research. Since joining the VRC, Dr. Seder has focused his efforts on understanding how the magnitude and quality of T cells influences protection and the role of adjuvants in shaping humoral and cellular immunity. Dr. Seder is internationally recognized in the field of cellular immunology and is held in high esteem by his colleagues. He currently serves as chief of the VRC Cellular Immunology Section.
Quinn, KM , Costa, AD, Yamamoto, A, Berry, D, Lindsay, RWB, Darrah, PA, Wang, L, Cheng, C, Kong, WP, Gall, JGD, Nicosia, A, Folgori, A, Colloca, S, Cortese, R, Gostick, E, Price, DA, Gomez, CE, Esteban, M, Wyatt, LS, Moss, B, Morgan, C, Roederer, M, Bailer, RT, Nabel, GJ, Koup, RA and Seder, RA. Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus gag-specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant adenoviral vector immunization. Journal of Immunology, 190(6):2720-35, 2013.
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; the VRC 312 Study Team. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science. 341(6152):1359-65, 2013.
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 Oct 28;334(6055):475-80. *Co-senior communicating author.
Kastenmüller K, Wille-Reece U, Lindsay RW, Trager LR, Darrah PA, Flynn BJ, Becker MR, Udey MC, Clausen BE, Igyarto BZ, Kaplan DH, Kastenmüller W, Germain RN, Seder RA. Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets. J Clin Invest. 2011 May;121(5):1782-96.
Flynn BJ, Kastenmüller K, Wille-Reece U, Tomaras GD, Alam M, Lindsay RW, Salazar AM, Perdiguero B, Gomez CE, Wagner R, Esteban M, Park CG, Trumpfheller C, Keler T, Pantaleo G, Steinman RM, Seder R. Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):7131-6.
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 Jul;13(7):843-50.
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Last Updated July 17, 2013