This resource provides unique primate reagents and services not available commercially in support of NIH funded investigators using nonhuman primates (NHP) as pre-clinical models for vaccine efficacy and immunotherapies. State of the art investigations of immune responses related to human infectious diseases, autoimmune diseases, organ and cell allogeneic and xenogeneic transplantation models or immunization procedures that use nonhuman primate models increasingly include the use of recombinant cytokines, chemokines, growth factors or immunomodulatory ligands in vivo. While the close evolutionary relationship between human and nonhuman primates results in cross reactivity between most human recombinant factors when used with NHP cells, differences in affinity/bioactivity have been noted. More important however, most NHP molecules are not identical to human homologues, often leading to the development of neutralizing antibody responses to the xenogeneic molecule in vivo, markedly restricting the repeated and most optimal in vivo use of select immunomodulators in these models. The ready availability of standardized purified recombinant NHP reagents has largely alleviated this limitation and allowed investigators to address seminal questions using NHP during the past 7 years of funding. In addition, testing of in vivo administration of these reagents has markedly revised the clinical administration schedule, leading to more tolerable and efficacious dosing. Thus, this application requests continued support for allowing this Resource to provide NHP factors, in DNA and protein form. Specifically, the resource will perform the following: 1. Continuation and expansion of preparation, testing and distribution of NHP cytokines/chemokines and soluble receptors in protein and recombinant DNA expression vectors. 2. Characterization and in vivo testing of soluble cytokine receptors as immune modulatory enhancers. 3. Generation of IgG and IgA Fc fusion molecules for differential targeting of cytokines to systemic vs. mucosal sites for enhanced localized immunomodulation. 4. Generation of polyclonal antibodies to NHP cytokines for which monoclonal antibodies are lacking.

Public Health Relevance

(provided by applicant): The goals of this grant are to continue and to expand the services and reagents provided by this unique resource to investigators using nonhuman primates as preclinical models for human disease and (immuno) therapy. To validate the data in the monkey model, the use of monkey reagents rather than human ones are imperative to avoid bias introduced by the use of heterologous reagents. Hence the need for the proposed services and reagents

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Resource-Related Research Projects (R24)
Project #
5R24OD010947-12
Application #
8435391
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Moro, Manuel H
Project Start
2002-04-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
12
Fiscal Year
2013
Total Cost
$474,190
Indirect Cost
$204,764
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Silveira, Eduardo L V; Rogers, Kenneth A; Gumber, Sanjeev et al. (2017) Immune Cell Dynamics in Rhesus Macaques Infected with a Brazilian Strain of Zika Virus. J Immunol 199:1003-1011
Hong, Jung J; Silveira, Eduardo L di Volpe; Amancha, Praveen K et al. (2017) Early initiation of antiretroviral treatment postSIV infection does not resolve lymphoid tissue activation. AIDS 31:1819-1824
Hong, Jung Joo; Chang, Kyu-Tae; Villinger, Francois (2016) The Dynamics of T and B Cells in Lymph Node during Chronic HIV Infection: TFH and HIV, Unhappy Dance Partners? Front Immunol 7:522
Li, Shengbin; Folkvord, Joy M; Rakasz, Eva G et al. (2016) Simian Immunodeficiency Virus-Producing Cells in Follicles Are Partially Suppressed by CD8+ Cells In Vivo. J Virol 90:11168-11180
Gumber, Sanjeev; Nascimento, Fernanda S; Rogers, Kenneth A et al. (2016) Experimental transfusion-induced Babesia microti infection: dynamics of parasitemia and immune responses in a rhesus macaque model. Transfusion 56:1508-19
Byrareddy, Siddappa N; Arthos, James; Cicala, Claudia et al. (2016) Sustained virologic control in SIV+ macaques after antiretroviral and ?4?7 antibody therapy. Science 354:197-202
Velu, Vijayakumar; Mylvaganam, Geetha Hanna; Gangadhara, Sailaja et al. (2016) Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells. J Immunol 197:1832-42
Ofotokun, Ighovwerha; Titanji, Kehmia; Vunnava, Aswani et al. (2016) Antiretroviral therapy induces a rapid increase in bone resorption that is positively associated with the magnitude of immune reconstitution in HIV infection. AIDS 30:405-14
Clark, Kristina B; Hsiao, Hui-Mien; Bassit, Leda et al. (2016) Characterization of dengue virus 2 growth in megakaryocyte-erythrocyte progenitor cells. Virology 493:162-72
Bialas, Kristy M; Tanaka, Takayuki; Tran, Dollnovan et al. (2015) Maternal CD4+ T cells protect against severe congenital cytomegalovirus disease in a novel nonhuman primate model of placental cytomegalovirus transmission. Proc Natl Acad Sci U S A 112:13645-50

Showing the most recent 10 out of 23 publications