当前位置: X-MOL 学术Mol. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
MVAΔ008 viral vector encoding the model protein OVA induces improved immune response against the heterologous antigen and equal levels of protection in a mice tumor model than the conventional MVA
Molecular Immunology ( IF 3.2 ) Pub Date : 2021-09-01 , DOI: 10.1016/j.molimm.2021.08.004
María Paula Del Médico Zajac 1 , Paula Molinari 1 , María José Gravisaco 1 , Daniel Omar Maizon 2 , Gabriel Morón 3 , María Magdalena Gherardi 4 , Gabriela Calamante 1
Affiliation  

Modified vaccinia Ankara virus (MVA) is extensively used as a vaccine vector. We have previously observed that MVAΔ008, an MVA lacking the gene that codes for interleukin-18 binding protein, significantly increases CD8+ and CD4+ T-cell responses to vaccinia virus (VACV) epitopes and recombinant HIV antigens. However, the efficacy of this vector against pathogens or tumor cells remains unclear. Thus, the aim of this study was to evaluate the cellular immune response and the protection induced by recombinant MVAs encoding the model antigen ovalbumin (OVA). We used the MO5 melanoma tumor model (OVA-expressing tumor) as an approach for evaluating the vector-induced efficacy. Our results show that MVAΔ008-OVA (optimized vector) induced higher in vivo specific cytotoxicity and ex vivo T-cell IFN-γ responses against OVA than the conventional MVA vector. Importantly, the recombinant vectors were capable of controlling MO5 tumor growth. Indeed, the administration of MVAΔ008-OVA or MVA-OVA in prophylactic and therapeutic schemes provided total protection and longer survival of mice, respectively. Overall, our results demonstrate the improved immunogenicity and the protective capacity of MVAΔ008 against a heterologous model antigen. These findings suggest that MVAΔ008 constitutes an excellent candidate for vaccine development against pathogens or cancer therapy.



中文翻译:

与传统 MVA 相比,编码模型蛋白 OVA 的 MVAΔ008 病毒载体在小鼠肿瘤模型中诱导改善的针对异源抗原的免疫反应和同等水平的保护

改良痘苗安卡拉病毒 (MVA) 被广泛用作疫苗载体。我们之前已经观察到 MVAΔ008(一种缺乏编码白细胞介素 18 结合蛋白的基因的 MVA)显着增加 CD8+ 和 CD4+ T 细胞对痘苗病毒 (VACV) 表位和重组 HIV 抗原的反应。然而,该载体对病原体或肿瘤细胞的功效仍不清楚。因此,本研究的目的是评估由编码模型抗原卵清蛋白 (OVA) 的重组 MVA 诱导的细胞免疫反应和保护。我们使用 MO5 黑色素瘤肿瘤模型(表达 OVA 的肿瘤)作为评估载体诱导功效的方法。我们的结果表明,MVAΔ008-OVA(优化载体)诱导更高的体内特异性细胞毒性和离体与传统 MVA 载体相比,T 细胞 IFN-γ 对 OVA 的反应。重要的是,重组载体能够控制 MO5 肿瘤生长。实际上,在预防和治疗方案中施用 MVAΔ008-OVA 或 MVA-OVA 分别为小鼠提供了全面保护和更长的存活时间。总的来说,我们的结果证明了 MVAΔ008 对异源模型抗原的免疫原性和保护能力的提高。这些发现表明 MVAΔ008 是开发针对病原体或癌症治疗的疫苗的极好候选者。

更新日期:2021-09-02
down
wechat
bug