Sasaki S, Amara R R, Oran A E, Smith J M, Robinson H L
Division of Microbiology and Immunology, Yerkes Regional Primate Research Center of Emory University, Atlanta, GA 30329, USA.
Nat Biotechnol. 2001 Jun;19(6):543-7. doi: 10.1038/89289.
Apoptotic bodies can be used to target delivery of DNA-expressed immunogens into professional antigen-presenting cells (APCs). Here we show that antigen-laden apoptotic bodies created by vectors co-expressing influenza virus hemagglutinin (HA) or nucleoprotein (NP) genes and mutant caspase genes markedly increased T-cell responses. Both CD8 and CD4 T-cell responses were affected. The adjuvant activity was restricted to partially inactivated caspases that allowed immunogen expression before the generation of apoptotic bodies. Active-site mutants of murine caspase 2 and an autocatalytic chimera of murine caspase 2 prodomain and human caspase 3 induced apoptosis that did not interfere with immunogen expression. The adjuvant activity also enhanced B-cell responses, but to a lesser extent than T-cell responses. The large increases in T-cell responses represent one of the strongest effects to date of a DNA adjuvant on cellular immunity.
凋亡小体可用于将DNA表达的免疫原靶向递送至专职抗原呈递细胞（APC）。在此，我们表明，由共表达流感病毒血凝素（HA）或核蛋白（NP）基因与突变型半胱天冬酶基因的载体产生的负载抗原的凋亡小体显著增强了T细胞反应。CD8和CD4 T细胞反应均受到影响。佐剂活性仅限于部分失活的半胱天冬酶，其允许在凋亡小体产生之前表达免疫原。小鼠半胱天冬酶2的活性位点突变体以及小鼠半胱天冬酶2前结构域与人半胱天冬酶3的自催化嵌合体诱导的凋亡不会干扰免疫原表达。佐剂活性还增强了B细胞反应，但程度低于T细胞反应。T细胞反应的大幅增加代表了迄今为止DNA佐剂对细胞免疫最强的作用之一。
