Major Areas of Research
- Vaccines against HIV, malaria, TB and cancer.
- Th1 and CD8+ T-cell memory
- Innate immunity, toll-like receptor adjuvants, and dendritic cell targeting
The aim of the Cellular Immunology Section (CIS) is to provide a mechanistic basis for developing vaccines for diseases that require humoral and cellular immunity. The specific focus is on preventive vaccines against HIV, malaria and tuberculosis and therapeutic vaccines against cancer.
Based on the critical role of CD4 and CD8 T cells in mediating protection against infections and tumors, a major area of study is to understand how various vaccine platforms influence the magnitude, quality, breadth and tissue distribution following immunization. This work uses recombinant viral, protein/adjuvant, and attenuated whole organism approaches. T-cell responses are assessed with a variety of technologies including multi-parameter flow cytometry, microfluidics (Fluidigm), and RNAseq. To understand the cellular and molecular mechanisms by which vaccines and immune adjuvants influence T cell immunity in vivo, we study the tropism of the vaccines or adjuvants for specific dendritic cell subsets and combine this with a global assessed of innate immunity by gene profiling.
The laboratory has a major focus on determining how different immune adjuvants influence humoral and cellular immunity when administered with protein or peptide antigens. Recent work has focused on using polymer chemistry and other bio-engineering approaches with specific toll-like receptor ligands (TLR) to optimize the delivery HIV, RSV or FLU protein antigens to optimize antibody responses and tumor specific neo-antigens to enhance T cell immunity.
Translation: To show how the different vaccines approaches mediate protection, experimental mouse and nonhuman primate models of infections such as Leishmania major, Mycobacterium tuberculosis, Listeria monocytogenes, malaria, and HIV/SIV infection are used. Moreover, we recently showed that an attenuated whole sporozoite malaria vaccine confers long-term protection in humans in a small number of subjects. Ongoing work is determining the immune correlates and mechanism of protection. This work is now being extended to a Phase II efficacy trial in African infants.
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.
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 ML, Ruben AJ, Li T, Eappen AG, Stafford RE, KC N, Murshedkar T, DeCederfelt H, Plummer SH, Hendel CS, Novik L, Costner PJM, Saunders JG, Laurens MB, Plowe CV, Flynn B, Whalen WR, Todd JP, Noor J, Rao S, Sierra-Davidson K, Lynn GM, Epstein JE, Kemp M, Fahle GA, Mikolajczak SA, Fishbaugher M, Sack BK, Kappe SHI, Davidson SA, Garver LS, Björkström NK, Nason MC, Graham BS, Roederer M, Kim Lee Sim B, Hoffman SL, Ledgerwood JE and Seder RA, for the VRC 312 and VRC 314 Study Teams. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination. Nature Medicine, 2016 (In Press).
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, Kastenmüller 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 polymer-linked TLR agonists that enhance vaccine immunogenicity. Nature Biotechnology, 33(11):1201-10, 2015.
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.