Robert Seder, M.D.
Cellular Immunology Section
Description of Research Program
The aim of the Cellular Immunology Laboratory is to rationally design vaccines for diseases that require cellular immunity in humans. The studies are focused into four integrated areas.
- Define T cell immune correlates of protection following vaccination. This work involves using a variety of vaccine platforms (recombinant viral vaccines and protein/adjuvant vaccines to elicit T cell immunity that confers varying protection. To assess the mechanisms by which T cells mediate protection a variety of assays are used. This includes multi-parameter flow cytometry to determine the phenotype and functional capacity of T cell responses at the single cell level. In addition, gene profiling of antigen specific T cells is used to define novel effector proteins that influence protection.
- Understand the cellular and molecular mechanisms by which viral vaccines and adjuvants induce adaptive immunity in vivo through their influence on innate cytokines and dendritic cells. For these studies, emphasis is directed at the tropism of the vaccines or adjuvants for specific dendritic cell subsets and how these influence antibody and T cell immunity. The vaccines used include recombinant replication defective adenovirus and poxvirus vaccines as well as multiple toll-like receptor ligands.
- Design novel protein/adjuvant platforms for inducing potent humoral and cellular immune responses. In these studies, 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 how 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.
- Develop experimental mouse and non-human primate models for infections requiring cellular immunity. To apply the knowledge learned from the areas highlighted above, we use experimental mouse and non-human primate models of Leishmania major, Mycobacterium tuberculosis, Listeria monocytogenes, Malaria and HIV/SIV infection.
Selected Publications
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. Attenuated Malaria Vaccine Designed to Protect through Hepatic CD8+ T Cell Immunity. Science, (In Press) 2011.
Kastenmüller, K, Wille-Reece. U, Lindsay, RWB, Trager, L, Darrah, P, Flynn, BJ, Becker, MR, Udey, MC, Clausen, BE, Igyarto, BZ, Kaplan, DH, Kastenmüller, W, Germain, RN and Seder, RA. Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets. Journal of Clinical Investigation, 121(5):1782-96, 2011.
Flynn, BJ, Kastenmüller, K, Wille-Reece. U, Tomaras, GD, Alam, SM, Lindsay, RWB, Salazar, AM, Perdiguero, B, Gomez, CE, Wagner, R, Esteban, M, Park, CG, Trumpfheller, C, Keler, T, Pantaleo, G, Steinman, RM and Seder, RA: Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Immunization with HIV Gag targeted to dendritic cells followed by recombinant New York vaccinia virus induces robust T-cell immunity in nonhuman primates. Proc Nat Acad Sci, 108(17):7131-6, 2011.
Lindsay RW, Darrah PA, Quinn KM, Wille-Reece U, Mattei LM, Iwasaki A, Kasturi SP, Pulendran B, Gall JG, Spies AG, Seder RA. CD8+ T cell responses following replication-defective adenovirus serotype 5 immunization are dependent on CD11c+ dendritic cells but show redundancy in their requirement of TLR and nucleotide-binding oligomerization domain-like receptor signaling. J Immunol. 185(3):1513-21, 2010.
Coffman RL, Sher A, Seder RA. Vaccine Adjuvants: Putting Innate Immunity to Work. Immunity. 33(4):492-503, 2010.
Tewari K, Flynn BJ, Boscardin SB, Kastenmueller K, Salazar AM, Anderson CA., Soundarapandian V, Keler T, Hoffman SL, Nussenzweig MC, Steinman RM, Seder R.A. Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and aDEC-CSP in Non Human Primates. Vaccine. 28(45):7256-66, 2010.
Darrah PA, Hegde ST, Patel DT, Lindsay RW, Chen L, Roederer, M. and Seder, R.A. IL-10 production Differentially Influences the magnitude, quality and protective capacity of Th1 responses depending on the vaccine platform. J Exp Med. 207(7):1421-33, 2010.
Seder RA, Darrah PA, Roederer M. T Cell Quality and Immune Memory: Implications for Vaccine Design. Nature Rev Immunol. 8: 247-58, 2008.
Darrah PA, Patel DT, DeLuca PM, Lindsay R, Davey DF, Flynn BJ, Hoff ST, Anderson P, Reed SG, Morris SL, Roederer M, Seder RA. Multifunctional Th1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nature Med. 13: 843-50, 2007.
Wille-Reece U, Flynn BJ, Loré K, Koup RA, Miles AP, Saul A, Kedl RM, Mattapallil JJ, Weiss WR, Roederer M, Seder RA. TLR agonists influence the magnitude and quality of Th1 and CD8+ memory cell responses following prime-boost immunization in non-human primates. J Exp Med. 203:1249-58, 2006.
Wille-Reece U, Flynn BJ, Lore K, Koup RA, Kedl RM, Mattapallil JJ, Weiss WR, Roederer M, Seder RA. HIV Gag protein conjugated to a TLR7/8 agonist influences the magnitude and quality of Th1 and CD8+ T cell responses in non-human primates. Proc Natl Acad Sci. 102,15190-15194, 2005.
If you are interested in a Research Fellowship, please send your CV to:
Dr. Robert A. Seder
NIH/Vaccine Research Center
40 Convent Drive
Bldg. 40, Room 3504
Bethesda, MD 20892-3025
back to top