Bates François A, Duncan Elizabeth H, Simmons Monika, Robinson Tanisha, Samineni Sridhar, Strbo Natasa, Villasante Eileen, Bergmann-Leitner Elke, Wijayalath Wathsala
Veterinary Services Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
Immunology Core/Malaria Biologics Branch, Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.
PeerJ. 2021 Mar 8;9:e10955. doi: 10.7717/peerj.10955. eCollection 2021.
Non-human primates (NHPs) play an important role in biomedical research, where they are often being re-used in multiple research studies over the course of their life-time. Researchers employ various study-specific screening criteria to reduce potential variables associated with subsequent re-use of NHPs. However, criteria set for NHP re-assignments largely neglect the impact of previous exposures on overall biology. Since the immune system is a key determinant of overall biological outcome, an altered biological state could be predicted by monitoring global changes in the immune profile. We postulate that every different exposure or a condition can generate a unique global immune profile in NHPs.
Changes in the global immune profile were evaluated in three different groups of rhesus macaques previously enrolled in dengue or malaria vaccine studies over six months after their last exposure. Naïve animals served as the baseline. Fresh blood samples were stained with various immune cell surface markers and analyzed by multi-color flow-cytometry to study immune cell dynamics in the peripheral blood. Serum cytokine profile in the pre-exposed animals were analyzed by mesoscale assay using a customized U-PLEX NHP biomarker panel of 12 cytokines/chemokines.
Pre-exposed macaques showed altered dynamics in circulating cytokines and certain innate and adaptive immune cell subsets such as monocytes, HLA-DR+NKT cells, B cells and T cells. Some of these changes were transient, while some lasted for more than six months. Each group seemed to develop a global immune profile unique to their particular exposure.
Our data strongly suggest that re-used NHPs should be evaluated for long-term, overall immunological changes and randomly assigned to new studies to avoid study bias.
非人灵长类动物（NHPs）在生物医学研究中发挥着重要作用，在其生命周期内常被多次用于多项研究。研究人员采用各种针对特定研究的筛选标准，以减少与NHPs后续再利用相关的潜在变量。然而，为NHP重新分配设定的标准在很大程度上忽略了先前暴露对整体生物学的影响。由于免疫系统是整体生物学结果的关键决定因素，通过监测免疫谱的全局变化可以预测生物状态的改变。我们推测，每一种不同的暴露或状况都能在NHPs中产生独特的全局免疫谱。
在三组先前参与登革热或疟疾疫苗研究的恒河猴中，评估其最后一次暴露后六个月内全局免疫谱的变化。未经暴露的动物作为基线。新鲜血液样本用各种免疫细胞表面标志物染色，并通过多色流式细胞术进行分析，以研究外周血中的免疫细胞动态。使用包含12种细胞因子/趋化因子的定制U-PLEX NHP生物标志物面板，通过中尺度分析对外暴露动物的血清细胞因子谱进行分析。
预先暴露的猕猴在循环细胞因子以及某些固有和适应性免疫细胞亚群（如单核细胞、HLA-DR+NKT细胞、B细胞和T细胞）中表现出动态变化。其中一些变化是短暂的，而有些则持续超过六个月。每组似乎都形成了与其特定暴露相关的独特全局免疫谱。
我们的数据强烈表明，对于重复使用的NHPs，应评估其长期的整体免疫学变化，并随机分配到新的研究中，以避免研究偏差。
