Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.
Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.
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DOI：
10.1371/journal.pone.0186079
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Luo M
中科院分区：
文献类型：
--
作者：
Li H;Nykoluk M;Li L;Liu LR;Omange RW;Soule G;Schroeder LT;Toledo N;Kashem MA;Correia-Pinto JF;Liang B;Schultz-Darken N;Alonso MJ;Whitney JB;Plummer FA;Luo M
食蟹猴是HIV疫苗研究中越来越重要的非人灵长类动物模型。通常需要没有预先存在的抗SIV免疫应答的无SIV动物来评估疫苗诱导的针对疫苗表位的免疫应答的效果。在此，为了选择这些动物进行疫苗研究，我们使用Bio-ELISA多重系统筛选了108只未处理的雌性猕猴的SIV抗原天然（基线）抗体。抗原包括分别与12个SIV蛋白酶切割位点（-10/+10）重叠的12个20聚体肽（PCS肽）和3个非PCS Gag或Env肽。在猴的亚群中检测到SIV抗原的天然抗体。使用纯化的重组SIV Gag和Env蛋白通过Western印迹进一步证实抗体对SIV的反应性。正如预期的那样，用PCS抗原免疫猴子引起抗PCS抗体。然而，出乎意料的是，也诱导了针对非PCS肽的抗体，如生物印迹和蛋白质印迹分析所示，而非PCS肽与PCS肽不共享序列同源性。在动物选择、实验设计和结果解释中，应考虑到在猕猴中存在天然和疫苗交叉诱导的SIV抗体，以使其最好地用于HIV疫苗研究。
Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10), respectively (PCS peptides), and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.
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