The goal of this Core is to establish novel single cell technology to analyze specific plasmablasts during an ongoing immune response to SIV vaccinafion or infecfion in rhesus macaques. We will generate detailed informafion 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 targetted by the plasmablasts and define the affinity/avidity ofthe indivdual anfibodies against their antigen. Furthermore we will characterize the funcfional propoerties ofthe isolated antibodies with regards to neutralizafion, breadth of neutralizafion as well as non-neutralizing, antibody mediated cytolyfic mechanisms. Furthermore, particularly interesting monoclonal antibodies, i.e. broadly neutralizing, might also be excellent candidates for future passive transfer experiements in rhesus macaques and also have implicafions 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 #
5U19AI096187-04
Application #
8681323
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Emory University
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Kasturi, Sudhir Pai; Kozlowski, Pamela A; Nakaya, Helder I et al. (2017) Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5? Restrictive Macaques. J Virol 91:
Chamcha, Venkateswarlu; Kannanganat, Sunil; Gangadhara, Sailaja et al. (2016) Strong, but Age-Dependent, Protection Elicited by a Deoxyribonucleic Acid/Modified Vaccinia Ankara Simian Immunodeficiency Virus Vaccine. Open Forum Infect Dis 3:ofw034
Cartwright, Emily K; Spicer, Lori; Smith, S Abigail et al. (2016) CD8(+) Lymphocytes Are Required for Maintaining Viral Suppression in SIV-Infected Macaques Treated with Short-Term Antiretroviral Therapy. Immunity 45:656-668
Yu, Cuiling; Liu, Yanling; Chan, Justin Tze Ho et al. (2016) Identification of human plasma cells with a lamprey monoclonal antibody. JCI Insight 1:
Havenar-Daughton, Colin; Reiss, Samantha M; Carnathan, Diane G et al. (2016) Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique. J Immunol 197:994-1002
Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja et al. (2016) High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5?-Restrictive Macaques. J Immunol 197:3586-3596
Locci, Michela; Wu, Jennifer E; Arumemi, Fortuna et al. (2016) Activin A programs the differentiation of human TFH cells. Nat Immunol 17:976-84
Smith, S Abigail; Kilgore, Katie M; Kasturi, Sudhir Pai et al. (2016) Signatures in Simian Immunodeficiency Virus SIVsmE660 Envelope gp120 Are Associated with Mucosal Transmission but Not Vaccination Breakthrough in Rhesus Macaques. J Virol 90:1880-7
Cho, Alice; Wrammert, Jens (2016) Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine. Curr Opin Virol 17:110-5
Santangelo, Philip J; Rogers, Kenneth A; Zurla, Chiara et al. (2015) Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods 12:427-32

Showing the most recent 10 out of 51 publications