Nonhuman Primate Models of Human Immunology

Messaoudi, Ilhem; Estep, Ryan D.; Robinson, Bridget A.; Wong, Scott W.

doi:10.1089/ars.2010.3241

Cited by 132 publications

(109 citation statements)

References 108 publications

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“…In this case, the desired clinical benefit is enhanced survival or prevention of major morbidity after exposure to potentially lethal doses of radiation across the hematopoietic acute radiation subsyndrome (USFDA 2014a). The non-human primate (NHP), rhesus macaque, is a relevant animal for the development of models that mimic the human response to the acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE) as well as treatment of the hematopoietic (H)-ARS, the gastrointestinal (GI)-ARS, immune reconstitution, prolonged GI damage, and delayed lung injury characteristic of the delayed effects DEARE (Monroy et al 1986;Gibbs et al 2007;Nikolich-Zugich 2007;MacVittie et al 2012aMacVittie et al and b, 2014MacVittie et al , 2015Farese et al 2012a;Herodin et al 2005;Messaoudi et al 2011;Garofalo et al 2014a and b;Hankey et al 2015;Thrall et al 2013Thrall et al , 2015. In this regard, the NHP, a well-characterized model, is a likely choice for defining the efficacy of MCM and conducting pivotal efficacy studies under the criteria of the FDA AR.…”

Section: Introductionmentioning

confidence: 99%

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques

MacVittie

Farese²,

Jackson³

2015

Health Physics

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Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432...

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Section: Introductionmentioning

confidence: 99%

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques

MacVittie

Farese²,

Jackson³

2015

Health Physics

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“…Previous studies performed in rhesus macaques have shown that transitional and effector memory subsets are present within the CD28+ CD95+ population and can be identified by including an additional phenotypic marker, such as CCR7 [24,25]. Thus, the delineation of specific memory T cell populations according to CD95 and CD28 expression alone may not accurately define true central and effector memory T cells subsets.…”

Section: Resultsmentioning

confidence: 99%

Transient global T cell activation after vaccination of rhesus macaques with a DNA-poxvirus vaccine regimen for HIV

Soares

Müller

Chege

et al. 2015

Vaccine

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“…Rhesus macaques and baboons both share a high degree of sequence similarity with humans, but do not have MHC-C loci (Messaoudi et al, 2011;Moffett and Loke, 2006;Prillman et al, 1996). Depending on the specific allele, rhesus macaques share an 80%-99% sequence identity with humans at the HLA loci (Doerks et al, 2002).…”

Section: Comparative Sequence Identity and Functionality Of The Majormentioning

confidence: 99%

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

Grow¹,

McCarrey²,

Navara³

2016

Stem Cell Research

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The derivation of dopaminergic neurons from induced pluripotent stem cells brings new hope for a patient-specific, stem cell-based replacement therapy to treat Parkinson's disease (PD) and related neurodegenerative diseases; and this novel cell-based approach has already proven effective in animal models. However, there are several aspects of this procedure that have yet to be optimized to the extent required for translation to an optimal cell-based transplantation protocol in humans. These challenges include pinpointing the optimal graft location, appropriately scaling up the graft volume, and minimizing the risk of chronic immune rejection, among others. To advance this procedure to the clinic, it is imperative that a model that accurately and fully recapitulates characteristics most pertinent to a cell-based transplantation to the human brain is used to optimize key technical aspects of the procedure. Nonhuman primates mimic humans in multiple ways including similarities in genomics, neuroanatomy, neurophysiology, immunogenetics, and age-related changes in immune function. These characteristics are critical to the establishment of a relevant model in which to conduct preclinical studies to optimize the efficacy and safety of cell-based therapeutic approaches to the treatment of PD. Here we review previous studies in rodent models, and emphasize additional advantages afforded by nonhuman primate models in general, and the baboon model in particular, for preclinical optimization of cell-based therapeutic approaches to the treatment of PD and other neurodegenerative diseases. We outline current unresolved challenges to the successful application of stem cell therapies in humans and propose that the baboon model in particular affords a number of traits that render it most useful for preclinical studies designed to overcome these challenges.

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Nonhuman Primate Models of Human Immunology

Cited by 132 publications

References 108 publications

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques

Transient global T cell activation after vaccination of rhesus macaques with a DNA-poxvirus vaccine regimen for HIV

Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson's disease

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