Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J Virol. 2013 Jul;87(13):7382-92. doi: 10.1128/JVI.00348-13. Epub 2013 Apr 24.
The live attenuated simian immunodeficiency virus (SIV) SIVmac239Δnef is the most effective SIV/human immunodeficiency virus (HIV) vaccine in preclinical testing. An understanding of the mechanisms responsible for protection may provide important insights for the development of HIV vaccines. Leveraging the uniquely restricted genetic diversity of Mauritian cynomolgus macaques, we performed adoptive transfers between major histocompatibility complex (MHC)-matched animals to assess the role of cellular immunity in SIVmac239Δnef protection. We vaccinated and mock vaccinated donor macaques and then harvested between 1.25 × 10(9) and 3.0 × 10(9) mononuclear cells from multiple tissues for transfer into 12 naive recipients, followed by challenge with pathogenic SIVmac239. Fluorescently labeled donor cells were detectable for at least 7 days posttransfer and trafficked to multiple tissues, including lung, lymph nodes, and other mucosal tissues. There was no difference between recipient macaques' peak or postpeak plasma viral loads. A very modest difference in viral loads during the chronic phase between vaccinated animal cell recipients and mock-vaccinated animal cell recipients did not reach significance (P = 0.12). Interestingly, the SIVmac239 challenge virus accumulated escape mutations more rapidly in animals that received cells from vaccinated donors. These results may suggest that adoptive transfers influenced the course of infection despite the lack of significant differences in the viral loads among animals that received cells from vaccinated and mock-vaccinated donor animals.
活减毒猴免疫缺陷病毒(SIV)SIVmac239Δnef 是临床前试验中最有效的 SIV/人类免疫缺陷病毒(HIV)疫苗。了解负责保护的机制可能为 HIV 疫苗的开发提供重要的见解。利用毛里求斯食蟹猕猴独特的受限遗传多样性,我们在主要组织相容性复合体(MHC)匹配的动物之间进行了过继转移,以评估细胞免疫在 SIVmac239Δnef 保护中的作用。我们对供体猕猴进行了疫苗接种和模拟疫苗接种,然后从多个组织中收获了 1.25×10(9)到 3.0×10(9)个单核细胞进行转移到 12 个未感染的受体中,然后用致病性 SIVmac239 进行挑战。荧光标记的供体细胞可至少在转移后 7 天检测到,并迁移到多个组织,包括肺、淋巴结和其他粘膜组织。受体猕猴的峰值或峰值后血浆病毒载量没有差异。疫苗接种动物细胞受体和模拟疫苗接种动物细胞受体之间在慢性期病毒载量的非常微小差异没有达到显著水平(P=0.12)。有趣的是,接受来自疫苗接种供体的细胞的动物中,SIVmac239 挑战病毒积累逃逸突变的速度更快。这些结果可能表明,尽管接受来自疫苗接种和模拟疫苗接种供体动物的细胞的动物之间的病毒载量没有显著差异,但过继转移仍影响了感染过程。