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
National Center for Research Resources (NCRR)
Type
Resource-Related Research Projects (R24)
Project #
2R24RR016988-09
Application #
7943387
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, Harold L
Project Start
2002-04-01
Project End
2015-02-28
Budget Start
2010-05-21
Budget End
2011-02-28
Support Year
9
Fiscal Year
2010
Total Cost
$519,644
Indirect Cost
Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Ryan, Emily S; Micci, Luca; Fromentin, RĂ©mi et al. (2016) Loss of Function of Intestinal IL-17 and IL-22 Producing Cells Contributes to Inflammation and Viral Persistence in SIV-Infected Rhesus Macaques. PLoS Pathog 12:e1005412
Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth A et al. (2014) Early lymphoid responses and germinal center formation correlate with lower viral load set points and better prognosis of simian immunodeficiency virus infection. J Immunol 193:797-806
Hong, Jung Joo; Amancha, Praveen K; Rogers, Kenneth et al. (2012) Spatial alterations between CD4(+) T follicular helper, B, and CD8(+) T cells during simian immunodeficiency virus infection: T/B cell homeostasis, activation, and potential mechanism for viral escape. J Immunol 188:3247-56
Lugli, Enrico; Mueller, Yvonne M; Lewis, Mark G et al. (2011) IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques. Blood 118:2520-9
Pallikkuth, Suresh; Rogers, Kenneth; Villinger, Francois et al. (2011) Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replication. Vaccine 29:9229-38
Dubie, Robert A; Maksaereekul, Saipiroon; Shacklett, Barbara L et al. (2009) Co-immunization with IL-15 enhances cellular immune responses induced by a vif-deleted simian immunodeficiency virus proviral DNA vaccine and confers partial protection against vaginal challenge with SIVmac251. Virology 386:109-21
Klatt, Nichole R; Villinger, Francois; Bostik, Pavel et al. (2008) Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. J Clin Invest 118:2039-49
Pereira, L E; Villinger, F; Wulff, H et al. (2007) Pharmacokinetics, toxicity, and functional studies of the selective Kv1.3 channel blocker 5-(4-phenoxybutoxy)psoralen in rhesus macaques. Exp Biol Med (Maywood) 232:1338-54
Ansari, Aftab A; Pereira, Lara E; Mayne, Ann E et al. (2007) The role of disease stage, plasma viral load and regulatory T cells (Tregs) on autoantibody production in SIV-infected non-human primates. J Autoimmun 28:152-9
Onlamoon, Nattawat; Plagman, Nicholas; Rogers, Kenneth A et al. (2007) Anti-CD3/28 mediated expansion of macaque CD4+ T cells is polyclonal and provides extended survival after adoptive transfer. J Med Primatol 36:206-18

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