The isolation of antibodies directly from immune donors offers the advantage of fully exploiting the strength of the human antibody response to vaccination or infection. By following the developmental fate of antigenspecific B cell populations through analysis of their antibodies we can generate a direct survey of B cell function. In this competitive renewal of our Technology Development Project (TOP) on Human Monoclonal Antibodies we combine two uniquely powerful new technologies recently developed that for the first time allow the efficient analysis of human B cell specificity en mass. One approach pioneered by Dr. Lanzavecchia, provides an analysis of the entire history of B cell specificities by efficiently producing mAbs from the long-term memory B cell compartment. The second technology from the Wilson and Ahmed laboratories scrutinizes current, ongoing plasmablast specificities and generates large numbers of antigenspecific antibodies in a short time that are predominantly specific to the antigens. We will use these tools to address fundamental questions about the human B cell response to yellow fever virus (YFV) and dengue virus. By combining these powerful platforms of generating human mAbs (plasmablasts and memory B cells) we should be able to comprehensively analyze the human B cell response to these viruses and to probe the relationship between memory B cells and antibody secreting plasma cells. Because the antibodies produced are fully human they can yield valuable diagnostics and allow for safer Pharmaceuticals than chimeric or humanized antibodies. Thus, in addition to addressing these fundamental questions, our proposed studies should also result in the development of a large panel of human mAbs against YFV and dengue - two flaviviruses that are of important public health concern and are high priority biodefense pathogens.
Three specific aims are proposed: 1) Characterize the primary human B cell response to YFV-17D leading to the generation of ASCs and long-term memory B cells;2) Analyze the dynamics, variable gene repertoire, and the specificity of ASC and memory cells induced by booster vaccination with YFV-17D. 3) Characterize the human B cell response to acute dengue virus infection of Children.

Public Health Relevance

The yellow fever and dengue viruses are emerging infectious diseases that are of important public health concern and are high priority biodefense pathogens. In addition to addressing a number of fundamental questions concerning the human immune response induced by these viruses, our proposed studies should also result in a large panel of human antibodies that may be used therapeutically for these viral infections.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
United States
Zip Code
Kim, C; Fang, F; Weyand, C M et al. (2017) The life cycle of a T cell after vaccination - where does immune ageing strike? Clin Exp Immunol 187:71-81
Goronzy, Jörg J; Weyand, Cornelia M (2017) Successful and Maladaptive T Cell Aging. Immunity 46:364-378
Wang, Taia T; Sewatanon, Jaturong; Memoli, Matthew J et al. (2017) IgG antibodies to dengue enhanced for Fc?RIIIA binding determine disease severity. Science 355:395-398
Kazmin, Dmitri; Nakaya, Helder I; Lee, Eva K et al. (2017) Systems analysis of protective immune responses to RTS,S malaria vaccination in humans. Proc Natl Acad Sci U S A 114:2425-2430
Yan, Yan; Qiu, Shangzhao; Jin, Zhuxuan et al. (2017) Detecting subnetwork-level dynamic correlations. Bioinformatics 33:256-265
Litzenburger, Ulrike M; Buenrostro, Jason D; Wu, Beijing et al. (2017) Single-cell epigenomic variability reveals functional cancer heterogeneity. Genome Biol 18:15
Bowen, James R; Quicke, Kendra M; Maddur, Mohan S et al. (2017) Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells. PLoS Pathog 13:e1006164
Corces, M Ryan; Trevino, Alexandro E; Hamilton, Emily G et al. (2017) An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods 14:959-962
Yanes, Rolando E; Gustafson, Claire E; Weyand, Cornelia M et al. (2017) Lymphocyte generation and population homeostasis throughout life. Semin Hematol 54:33-38
Schep, Alicia N; Wu, Beijing; Buenrostro, Jason D et al. (2017) chromVAR: inferring transcription-factor-associated accessibility from single-cell epigenomic data. Nat Methods 14:975-978

Showing the most recent 10 out of 227 publications