Li Hongzhao, Nykoluk Mikaela, Li Lin, Liu Lewis R, Omange Robert W, Soule Geoff, Schroeder Lukas T, Toledo Nikki, Kashem Mohammad Abul, Correia-Pinto Jorge F, Liang Binhua, Schultz-Darken Nancy, Alonso Maria J, Whitney James B, Plummer Francis A, Luo Ma
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
PLoS One. 2017 Oct 5;12(10):e0186079. doi: 10.1371/journal.pone.0186079. eCollection 2017.
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.
食蟹猕猴是用于HIV疫苗研究的一种越来越重要的非人类灵长类动物模型。通常需要没有预先存在的抗SIV免疫反应的无SIV动物来评估疫苗诱导的免疫反应针对疫苗表位的效果。在此，为了选择此类动物用于疫苗研究，我们使用Bio-Plex多重检测系统对108只未接触过抗原的毛里求斯雌性食蟹猕猴进行了SIV抗原天然（基线）抗体筛查。抗原包括分别与十二个SIV蛋白酶裂解位点（-10/+10）重叠的十二个20聚体肽（PCS肽），以及三个非PCS Gag或Env肽。在部分猴子中检测到了针对SIV抗原的天然抗体。使用纯化的重组SIV Gag和Env蛋白通过蛋白质印迹法进一步证实了对SIV的抗体反应性。正如预期的那样，用PCS抗原免疫猴子引发了抗PCS抗体。然而，出乎意料的是，蛋白质印迹法和Bio-Plex分析均显示，也诱导产生了针对非PCS肽的抗体，而这些非PCS肽与PCS肽没有序列同源性。在动物选择、实验设计和结果解释中应考虑毛里求斯食蟹猕猴中天然和疫苗交叉诱导的SIV抗体的存在情况，以便在HIV疫苗研究中充分利用它们。
