Corripio-Miyar Yolanda, MacLeod Clair Lyle, Mair Iris, Mellanby Richard J, Moore Barry D, McNeilly Tom N
Moredun Research Institute, Pentlands Science Park, Penicuik EH26 0PZ, UK.
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XQ, UK.
Vaccines (Basel). 2023 Jul 11;11(7):1229. doi: 10.3390/vaccines11071229.
Successful vaccines require adjuvants able to activate the innate immune system, eliciting antigen-specific immune responses and B-cell-mediated antibody production. However, unwanted secondary effects and the lack of effectiveness of traditional adjuvants has prompted investigation into novel adjuvants in recent years. Protein-coated microcrystals modified with calcium phosphate (CaP-PCMCs) in which vaccine antigens are co-immobilised within amino acid crystals represent one of these promising self-adjuvanting vaccine delivery systems. CaP-PCMCs has been shown to enhance antigen-specific IgG responses in mouse models; however, the exact mechanism of action of these microcrystals is currently unclear. Here, we set out to investigate this mechanism by studying the interaction between CaP-PCMCs and mammalian immune cells in an in vitro system. Incubation of cells with CaP-PCMCs induced rapid pyroptosis of peripheral blood mononuclear cells and monocyte-derived dendritic cells from cattle, sheep and humans, which was accompanied by the release of interleukin-1β and the activation of Caspase-1. We show that this pyroptotic event was cell-CaP-PCMCs contact dependent, and neither soluble calcium nor microcrystals without CaP (soluble PCMCs) induced pyroptosis. Our results corroborate CaP-PCMCs as a promising delivery system for vaccine antigens, showing great potential for subunit vaccines where the enhancement or find tuning of adaptive immunity is required.
成功的疫苗需要能够激活先天免疫系统、引发抗原特异性免疫反应和B细胞介导的抗体产生的佐剂。然而，传统佐剂存在不良的副作用且缺乏有效性，这促使近年来人们对新型佐剂展开研究。用磷酸钙修饰的蛋白质包被微晶（CaP-PCMCs），其中疫苗抗原共同固定在氨基酸晶体内，是这些有前景的自佐剂疫苗递送系统之一。在小鼠模型中，CaP-PCMCs已被证明能增强抗原特异性IgG反应；然而，这些微晶的确切作用机制目前尚不清楚。在此，我们通过研究CaP-PCMCs与哺乳动物免疫细胞在体外系统中的相互作用来探究这一机制。用CaP-PCMCs孵育细胞会诱导牛、羊和人的外周血单核细胞以及单核细胞衍生的树突状细胞快速发生焦亡，这伴随着白细胞介素-1β的释放和半胱天冬酶-1的激活。我们表明，这种焦亡事件依赖于细胞与CaP-PCMCs的接触，可溶性钙和不含CaP的微晶（可溶性PCMCs）均不会诱导焦亡。我们的结果证实CaP-PCMCs是一种有前景的疫苗抗原递送系统，对于需要增强或微调适应性免疫的亚单位疫苗显示出巨大潜力。
