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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-LR-A)
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Emory University
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