Robert Seder, M.D.

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.