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油佐剂增强犬腺病毒载体疫苗诱导的免疫应答。

An Oil-Based Adjuvant Improves Immune Responses Induced by Canine Adenovirus-Vectored Vaccine in Mice.

机构信息

UMR Virologie, INRAE, ANSES, EnvA, 94700 Maisons-Alfort, France.

SEPPIC Paris La Défense, 92250 La Garenne Colombes, France.

出版信息

Viruses. 2023 Jul 30;15(8):1664. doi: 10.3390/v15081664.

Abstract

There is a significant need for highly effective vaccines against emerging and common veterinary infectious diseases. Canine adenovirus type 2 (CAV2) vectors allow rapid development of multiple vaccines and have demonstrated their potential in animal models. In this study, we compared the immunogenicity of a non-replicating CAV2 vector encoding the rabies virus glycoprotein with and without Montanide ISA 201 VG, an oil-based adjuvant. All vaccinated mice rapidly achieved rabies seroconversion, which was associated with complete vaccine protection. The adjuvant increased rabies antibody titers without any significant effect on the anti-CAV2 serological responses. An RT Profiler™ PCR array was conducted to identify host antiviral genes modulated in the blood samples 24 h after vaccination. Functional analysis of differentially expressed genes revealed the up-regulation of the RIG-I, TLRs, NLRs, and IFNs signaling pathways. These results demonstrate that a water-in-oil-in-water adjuvant can shape the immune responses to an antigen encoded by an adenovirus, thereby enhancing the protection conferred by live recombinant vaccines. The characterization of early vaccine responses provides a better understanding of the mechanisms underlying the efficacy of CAV2-vectored vaccines.

摘要

目前,迫切需要针对新兴和常见的兽医传染病的高效疫苗。犬腺病毒 2 型(CAV2)载体允许快速开发多种疫苗,并在动物模型中证明了其潜力。在这项研究中,我们比较了编码狂犬病病毒糖蛋白的非复制 CAV2 载体与添加和不添加油包水佐剂 Montanide ISA 201 VG 的免疫原性。所有接种疫苗的小鼠均迅速实现狂犬病血清转化,这与完全疫苗保护相关。佐剂增加了狂犬病抗体滴度,而对抗 CAV2 的血清学反应没有任何显著影响。接种疫苗后 24 小时,通过 RT Profiler™ PCR 阵列鉴定了血液样本中调节的宿主抗病毒基因。差异表达基因的功能分析表明,RIG-I、TLRs、NLRs 和 IFNs 信号通路被上调。这些结果表明,水包油包水佐剂可以改变腺病毒编码抗原的免疫反应,从而增强活重组疫苗提供的保护。对早期疫苗反应的特征描述提供了对 CAV2 载体疫苗功效的机制的更好理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9618/10458467/581b1c8fe425/viruses-15-01664-g001.jpg

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