The goal of this Core is to establish novel single cell technology to analyze specific plasmablasts during an ongoing immune response to SIV vaccination or infection in rhesus macaques. We will generate detailed information about the dynamics, immunoglobulin isotype useage and phenotype of the plasmablast responses induced both at a systemic level as well as at mucosal sites, and determine how these responses are modulated by the use of different adjuvants. The single cell analysis will allow us to interrogate the immunoglobulin repertoire of the ongoing response, identify the specific epitopes targeted by the plasmablasts and define the affinity/avidity ofthe individual antibodies against their antigen. Furthermore we will characterize the functional properties ofthe isolated antibodies with regards to neutralization, breadth of neutralization as well as non-neutralizing, antibody mediated cytolytic mechanisms. Furthermore, particularly interesting monoclonal antibodies, i.e. broadly neutralizing, might also be excellent candidates for future passive transfer experiments in rhesus macaques and also have implications for therapy and vaccine design for HIV in humans.

Public Health Relevance

These studies will provide a single cell characterization of ongoing plasmablast responses after SIV vaccination or infection, both at a systemic and a mucosal level. The development of potent and broadly neutralizing antibodies isolated through this effort might have implications for HIV vaccine design and possibly treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096187-03
Application #
8516870
Study Section
Special Emphasis Panel (ZAI1-LR-A)
Project Start
2013-07-01
Project End
2016-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$329,890
Indirect Cost
$132,879
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yang, Rendong; Bai, Yun; Qin, Zhaohui et al. (2014) EgoNet: identification of human disease ego-network modules. BMC Genomics 15:314
Derdeyn, Cynthia A; Moore, Penny L; Morris, Lynn (2014) Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection. Curr Opin HIV AIDS 9:210-6
Basu, Debby; Xiao, Peng; Ende, Zachary et al. (2014) Low antibody-dependent cellular cytotoxicity responses in Zambians prior to HIV-1 intrasubtype C superinfection. Virology 462-463:295-8
Magri, Giuliana; Miyajima, Michio; Bascones, Sabrina et al. (2014) Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat Immunol 15:354-64
Yu, Tianwei; Jones, Dean P (2014) Improving peak detection in high-resolution LC/MS metabolomics data using preexisting knowledge and machine learning approach. Bioinformatics 30:2941-8
Li, Shuzhao; Rouphael, Nadine; Duraisingham, Sai et al. (2014) Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol 15:195-204
Romberg, Neil; Chamberlain, Nicolas; Saadoun, David et al. (2013) CVID-associated TACI mutations affect autoreactive B cell selection and activation. J Clin Invest 123:4283-93
Li, Shuzhao; Nakaya, Helder I; Kazmin, Dmitri A et al. (2013) Systems biological approaches to measure and understand vaccine immunity in humans. Semin Immunol 25:209-18
Pulendran, Bali; Oh, Jason Z; Nakaya, Helder I et al. (2013) Immunity to viruses: learning from successful human vaccines. Immunol Rev 255:243-55
Cerutti, Andrea; Cols, Montserrat; Puga, Irene (2013) Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes. Nat Rev Immunol 13:118-32

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