Hervas-Stubbs Sandra, Rueda Paloma, Lopez Lissette, Leclerc Claude
Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.
J Immunol. 2007 Feb 15;178(4):2361-9. doi: 10.4049/jimmunol.178.4.2361.
Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8(+) T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-alphabeta, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.
杆状病毒(BVs)是对昆虫具有致病性的双链DNA病毒。它们在全球范围内被用作选择性生物杀虫剂,并用于在昆虫细胞中生产重组蛋白。令人惊讶的是,尽管它们在研究和工业中广泛使用且在环境中传播,但这些昆虫病毒对哺乳动物免疫反应的潜在影响仍然完全未知。我们在本研究中表明,BVs在小鼠中具有强大的佐剂特性,可促进针对共同给药抗原的强效体液和CD8(+) T细胞适应性反应。BVs还可诱导树突状细胞在体内成熟并产生炎性细胞因子。我们证明,BVs在BV-昆虫细胞表达系统中产生的病毒样颗粒的强免疫原性中起主要作用。因此,在BV表达系统中产生的重组蛋白中即使存在少量BVs也可能增强这些蛋白的免疫特性。BVs的这种佐剂行为主要由IFN-αβ介导,尽管也涉及独立于I型IFN信号传导的机制。这项研究表明,非致病性昆虫病毒可能对哺乳动物免疫系统有强大影响。