Cellular Immunology Section
Robert Seder, M.D.
Provides direct clinical care to patients at NIH Clinical Center
Major Areas of Research
- Vaccines against Cancer, TB, malaria, and SARS-CoV-2
- Th1 and CD8+ T-cell memory
- Innate immunity, toll-like receptor adjuvants, and dendritic cell targeting
- Monoclonal antibodies against malaria
The aim of the Cellular Immunology Section (CIS) is to provide a mechanistic basis for developing preventive vaccines against HIV, malaria, tuberculosis, SARS-CoV-2 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 (e.g., 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-CoV-2. 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.
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. He is currently Chief of the Cellular Immunology Section in the Vaccine Research Center in the NIAID, NIH. Dr. Seder's laboratory has focused on the cellular and molecular mechanisms by which vaccines and adjuvants mediate protective immunity in mouse, and non-human primate models of HIV, Malaria, Tuberculosis and cancer. His work has demonstrated the importance of the quality of T cell responses in mediating protection against various infections and the importance of the route of vaccination in generating tissue resident T cells for protection against malaria and TB. Dr. Seder has translated his scientific discoveries and led the first in human clinical studies using intravenous vaccination to generate protective immunity with an attenuated malaria vaccine and recently showed that a monoclonal antibody he discovered can prevent malaria infection against intense seasonal transmission in African adults. Over the two years, Dr. Seder has helped lead the pre-clinical development of the Moderna mRNA vaccine against COVID. This provided pre-clinical data for demonstrating safety and efficacy of the Moderna vaccine in animals prior to the initiation of the pivotal Phase 3 study in humans and more recently provided the scientific basis for boosting humans with mRNA against variants.
Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium falciparum, in an Age De-Escalation, Dose-Escalation Trial and a Randomized, Placebo-Controlled, Double-Blind Trial of Children in Kenya, NCT05019729
Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Dose-Escalation Trial in Adults and Children and a Randomized, Double-Blind Trial of Children in Mali, NCT05304611
Wu RL, Idris AH, Berkowitz NM, Happe M, Gaudinski MR, Buettner C, Strom L, Awan SF, Holman LA, Mendoza F, Gordon IJ, Hu Z, Campos Chagas A, Wang LT, Da Silva Pereira L, Francica JR, Kisalu NK, Flynn BJ, Shi W, Kong WP, O'Connell S, Plummer SH, Beck A, McDermott A, Narpala SR, Serebryannyy L, Castro M, Silva R, Imam M, Pittman I, Hickman SP, McDougal AJ, Lukoskie AE, Murphy JR, Gall JG, Carlton K, Morgan P, Seo E, Stein JA, Vazquez S, Telscher S, Capparelli EV, Coates EE, Mascola JR, Ledgerwood JE, Dropulic LK, Seder RA; VRC 614 Study Team. Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria. NEJM. 2022 Aug 4;387(5):397-407.
Gagne M, Corbett KS, Flynn BJ, Foulds KE, Wagner DA, Andrew SF, Todd JM, Honeycutt CC, McCormick L, Nurmukhambetova ST, Davis-Gardner ME, Pessaint L, Bock KW, Nagata BM, Minai M, Werner AP, Moliva JI, Tucker C, Lorang CG, Zhao B, McCarthy E, Cook A, Dodson A, Teng IT, Mudvari P, Roberts-Torres J, Laboune F, Wang L, Goode A, Kar S, Boyoglu-Barnum S, Yang ES, Shi W, Ploquin A, Doria-Rose N, Carfi A, Mascola JR, Boritz EA, Edwards DK, Andersen H, Lewis MG, Suthar MS, Graham BS, Roederer M, Moore IN, Nason MC, Sullivan NJ, Douek DC, Seder RA. Protection from SARS-CoV-2 Delta one year after mRNA-1273 vaccination in rhesus macaques coincides with anamnestic antibody response in the lung. Cell. 2022 Jan 6;185(1):113-130.e15.
Corbett KS, Nason MC, Flach B, Gagne M, O'Connell S, Johnston TS, Shah SN, Edara VV, Floyd K, Lai L, McDanal C, Francica JR, Flynn B, Wu K, Choi A, Koch M, Abiona OM, Werner AP, Moliva JI, Andrew SF, Donaldson MM, Fintzi J, Flebbe DR, Lamb E, Noe AT, Nurmukhambetova ST, Provost SJ, Cook A, Dodson A, Faudree A, Greenhouse J, Kar S, Pessaint L, Porto M, Steingrebe K, Valentin D, Zouantcha S, Bock KW, Minai M, Nagata BM, van de Wetering R, Boyoglu-Barnum S, Leung K, Shi W, Yang ES, Zhang Y, Todd JM, Wang L, Alvarado GS, Andersen H, Foulds KE, Edwards DK, Mascola JR, Moore IN, Lewis MG, Carfi A, Montefiori D, Suthar MS, McDermott A, Roederer M, Sullivan NJ, Douek DC, Graham BS, Seder RA. Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science. 2021 Sep 17;373(6561):eabj0299.
Kassoum Kayentao, Aissata Ongoiba, Anne C. Preston, Sara A. Healy, Safiatou Doumbo, Didier Doumtabe, Abdrahamane Traore, Hamadi Traore, Adama Djiguiba, Shanping Li, Mary E. Peterson, Shinyi Telscher, Azza H. Idris, Neville K. Kisalu, Kevin Carlton, Leonid Serebryannyy, Sandeep Narpala, Adrian B. McDermott, Martin Gaudinski, Siriman Traore, Hamidou Cisse, Mamadou Keita, Jeff Skinner, Zonghui Hu, Amatigué Zéguimé, Adama Ouattara, M’Bouye Doucoure, Amagana Dolo, Abdoulaye Djimdé, Boubacar Traore, Robert A. Seder, and Peter D. Crompton, for the Mali Malaria mAb Trial Team*. Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali. NEJM. October 31, 2022.
Baharom F, Ramirez-Valdez RA, Khalilnezhad A, Khalilnezhad S, Dillon M, Hermans D, Fussell S, Tobin KKS, Dutertre CA, Lynn GM, Müller S, Ginhoux F, Ishizuka AS, Seder RA. Systemic vaccination induces CD8+ T cells and remodels the tumor microenvironment. Cell. 2022 Nov 10;185(23):4317-4332.e15
Darrah PA, Zeppa JJ, Maiello P, Hackney JA, Wadsworth MH 2nd, Hughes TK, Pokkali S, Swanson PA 2nd, Grant NL, Rodgers MA, Kamath M, Causgrove CM, Laddy DJ, Bonavia A, Casimiro D, Lin PL, Klein E, White AG, Scanga CA, Shalek AK, Roederer M, Flynn JL, Seder RA. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature. 2020 Jan;577(7788):95-102.
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The Cellular Immunology Section focuses on Coronavirus, Malaria, and Tuberculosis (TB).