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 major area of study is to define T-cell immune correlates of protection following vaccination and infection. 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 assessed by multi-parameter flow cytometry, microfluidics (Fluidigm), RNAseq, and assessment of antigenic breadth by epitope mapping in a variety of rodent and non-human primate models as well as from 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 as well as innate immunity that is induced by gene profiling. The vaccines used in the study include recombinant replication defective adenovirus and poxvirus vaccines, as well as protein and particle vaccines formulated with toll-like receptor ligands targeted to activate 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. Recent work has used 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 critical for developing vaccines against HIV.
Experimental mouse and nonhuman primate models of infections such as Leishmania major, Mycobacterium tuberculosis, Listeria monocytogenes, malaria, and HIV/SIV infection are used. There are now ongoing studies to assess the efficacy of an attenuated whole sporozoite malaria vaccine in humans and determine whether it confers durable protection. An important aspect of this work will be to define the immune mechanisms of protection using multiple technologies. These studies should provide insight into how to develop vaccines against infections that require breadth of antigens and effector T cell responses.
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.
Lynn GM, Laga R, Darrah PA, Ishizuka AS, Balaci AJ, Dulcey AE, Pechar M, Pola R, Gerner MY, Yamomoto A, Buechler CR, Quinn KM, Smelkinson MG, Vanek O, Cawood R, Hills Y, Vasalatiy O, Kastenmuller K, Francica JR, Stutts L, Tom JK, Ryu KA, Esser-Kahn AP, Etrych T, Fisher KD, Seymour LW, and Seder RA. In vivo characterization of the physiochemical properties of TLR agonist delivery that enhance vaccine immunogenicity. Nature Biotechnology 2015 (In Press).
Francica JR, Sheng Z, Zhang Z, Nishimura Y, Shingai M, Ramesh A, Keele BF, Schmidt SD, Flynn BJ, Darko S, Lynch RM, Yamamoto T, Matus-Nicodemos R, Wolinsky D, NISC Comparative Sequencing Program, Valiante NM, Malyala P, De Gregario E, Barnett SW, Singh M, O’Hagan DT, Koup RA, Mascola JR, Martin MA, Kepler TB, Douek DC, Shapiro L, and Seder RA. Analysis of peripheral immunoglobulin transcripts and somatic hypermutation following SHIV AD8 infection and HIV-1 Envelope protein and adjuvant vaccination in nonhuman primates. Nature Communications, 6:6565, 2015.
Quinn KM, Zak DE, Costa A, Yamamoto A, Kastenmüller K, Hill BJ, Lynn GM, Darrah PA, Lindsay RWB, Wong L, Cheng C, Nicosia A, Folgori A, Colloca S, Cortese R, Gostick E, Price DA, Gall JGD, Roederer M, Aderem A, and Seder RA. Antigen expression determines adenoviral vaccine potency, independent of IFN or STING signaling. Journal of Clinical Investigation, 125(3):1129-46, 2015.
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.
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Last Updated September 17, 2015