Instituto de Biotecnología, Centro Nacional de Investigaciones Agropecuarias, INTA Castelar, Nicolás Repetto y De Los Reseros S/N° (B1686IGC), Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Appl Microbiol Biotechnol. 2018 Dec;102(23):10139-10146. doi: 10.1007/s00253-018-9368-8. Epub 2018 Sep 20.
The baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects lepidopteran invertebrates as natural hosts, although it also has been used as display vector for vaccine development. In this work, we evaluated the effectiveness of repetitive doses of AcMNPV-based vectors on the cytotoxic immune response specific to the capsid-displayed heterologous antigen ovalbumin (OVA). Our results demonstrate that baculovirus vectors induce a boosting effect in the cytotoxic immune response to OVA, making possible to recover the levels obtained in the primary response. Moreover, mice preimmunized with wild-type baculovirus showed a complete lack of antigen-specific CD8 cytotoxic T lymphocytes (CTLs) that may be related to the presence of antibodies directed to baculoviral surface proteins, particularly to GP64. However, baculovirus was able to induce the innate immune response in spite of a previous response against this vector, although some quantitative differences reflect a distinct activation of the immune cells in prime and boost. This is the first report in which the novel capsid display strategy is evaluated in prime-boost schemes to improve efficient CTL responses.
杆状病毒 Autographa californica 多角体病毒 (AcMNPV) 作为天然宿主感染鳞翅目无脊椎动物,尽管它也被用作疫苗开发的展示载体。在这项工作中,我们评估了基于 AcMNPV 的载体的重复剂量对针对衣壳展示的异源抗原卵清蛋白 (OVA) 的细胞毒性免疫反应的有效性。我们的结果表明,杆状病毒载体诱导针对 OVA 的细胞毒性免疫反应的增强效应,使得有可能恢复初次反应中获得的水平。此外,用野生型杆状病毒预先免疫的小鼠表现出完全缺乏针对 OVA 的抗原特异性 CD8 细胞毒性 T 淋巴细胞 (CTL),这可能与针对杆状病毒表面蛋白,特别是 GP64 的抗体的存在有关。然而,尽管针对该载体存在先前的反应,但杆状病毒仍能够诱导先天免疫反应,尽管一些定量差异反映了在初次免疫和增强免疫中免疫细胞的不同激活。这是首次在初次-增强方案中评估新型衣壳展示策略以提高有效的 CTL 反应的报告。