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Experimental Autoimmune Encephalomyelitis (EAE) Model of Cynomolgus Macaques Induced by Recombinant Human MOG1-125 (rhMOG1-125) Protein and MOG34-56 Peptide

[ Vol. 24 , Issue. 12 ]

Author(s):

Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu* and Yunxiao Sun*   Pages 1166 - 1178 ( 13 )

Abstract:


Background: Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used in multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations.

Objectives: The main objective of this study was to establish an ideal EAE cynomolgus monkey model resembling human MS by immunizing human myelin oligodendrocyte glycoprotein (MOG) protein.

Methods: In this study, six female cynomolgus monkeys were divided into two separate experiment groups and one monkey as the control. EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) by subcutaneous multipoint immunization in the armpit and inguinal region and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (scoreā‰„2). The body weight, clinical scores, magnetic resonance imaging (MRI), histopathology, antibody, cytokine profiling and antigen-specific lymphocyte proliferation were evaluated.

Results: The results showed that despite the different time intervals between onset and significant neurological deficits, all the cynomolgus monkeys immunized with rhMOG1-125 or MOG34-56 developed clinically significant acute fulminant or mild forms of EAE, with a success rate of 100%. The clinical courses were obvious heterogeneity which closely resembles MS. MOG34-56 immunization was much milder compared with rhMOG1-125 immunized individuals, at least in cynomolgus monkeys. Inflammation and demyelinated lesions were present in the brains and spinal cords. Immune profiling revealed high IgG levels associated with early onset of EAE but not the course of the disease. Significant antigen-specific T lymphocyte responses against immunodominant epitopes of MOG were also detected.

Conclusion: Our results indicated rhMOG1-125 and MOG34-56 could induce successfully EAE models resembling MS in cynomolgus monkeys. The synergistic action of anti-myelin T cells and Abs during the pathogenesis of EAE could establish a more ideal EAE model.

Keywords:

Cynomolgus macaques, EAE, multiple sclerosis, MOG, autoimmunity, inflammation.

Affiliation:

Minigene Pharmacy Lab, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, Jiangsu, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Department of Pharmaceutical Engineering, School of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou , 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260, Minigene Pharmacy Lab, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, Jiangsu, Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Guangdong Institute of Applied Biological Resources, Guangzhou, 510260

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