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设计轮状病毒VP8与甲型肝炎病毒VP1的融合蛋白并评估BALB/c小鼠的免疫反应。

Designing the fusion protein of rotavirus VP8 and hepatitis A virus VP1 and evaluating the immunological response in BALB/c mice.

作者信息

Yarmohammadi Hassan, Aghasadeghi Mohammadreza, Akhavan Sepahi Abbas, Hamidi-Fard Mojtaba, Bahramali Golnaz

机构信息

Department of Microbiology, North Tehran Branch, Islamic Azad University, Tehran, Iran.

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Iran J Microbiol. 2024 Jun;16(3):401-410. doi: 10.18502/ijm.v16i3.15797.

Abstract

BACKGROUND AND OBJECTIVES

Rotavirus and Hepatitis A virus are responsible for causing gastroenteritis and jaundice. The current vaccination approaches have proven insufficient, especially in low-income countries. In this study, we presented a novel dual-vaccine candidate that combines the rotavirus VP8 protein and the hepatitis A virus VP1.

MATERIALS AND METHODS

The VP8*-rotavirus+AAY+HAV-VP1 fusion protein was produced using an expression system. The recombinant protein had a molecular weight of approximately 45.5 kDa and was purified through affinity chromatography. BALB/c mice were injected subcutaneously with the recombinant protein, VP1, VP8 and vaccines for rotavirus and hepatitis A virus, both with and without ALUM and M720 adjuvants. ELISA assays were used to measure total IgG, IgG1, IgG2, and short-term and long-term IL-5 and IFN-γ responses.

RESULTS

The fusion protein, when combined with adjuvants, elicited significantly higher total IgG, IgG1, and IgG2 responses compared to VP1 and VP8 alone, as well as the rotavirus and hepatitis A vaccines. Furthermore, it induced a higher short-term IL-5 and IFN-γ response while demonstrating a higher long-term IL-5 response compared to the rotavirus and hepatitis A vaccines.

CONCLUSION

This study demonstrates that the VP8*-rotavirus+AAY+HAV-VP1 fusion protein is a promising dual vaccine candidate for immunization against hepatitis A and rotaviruses.

摘要

背景与目的

轮状病毒和甲型肝炎病毒可引发肠胃炎和黄疸。目前的疫苗接种方法已被证明并不充分,尤其是在低收入国家。在本研究中,我们提出了一种新型双疫苗候选物,它结合了轮状病毒VP8蛋白和甲型肝炎病毒VP1。

材料与方法

使用表达系统生产VP8*-轮状病毒+AAY+甲型肝炎病毒-VP1融合蛋白。该重组蛋白的分子量约为45.5 kDa,并通过亲和层析进行纯化。将重组蛋白、VP1、VP8以及轮状病毒和甲型肝炎病毒疫苗分别皮下注射到BALB/c小鼠体内,同时使用和不使用铝佐剂和M720佐剂。采用ELISA检测法测量总IgG、IgG1、IgG2以及短期和长期的IL-5和IFN-γ反应。

结果

与单独的VP1和VP8以及轮状病毒和甲型肝炎疫苗相比,融合蛋白与佐剂联合使用时可引发显著更高的总IgG、IgG1和IgG2反应。此外,与轮状病毒和甲型肝炎疫苗相比,它诱导了更高的短期IL-5和IFN-γ反应,同时显示出更高的长期IL-5反应。

结论

本研究表明,VP8*-轮状病毒+AAY+甲型肝炎病毒-VP1融合蛋白是一种有前景的双疫苗候选物,可用于预防甲型肝炎和轮状病毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b92e/11245353/deb0904c8a1d/IJM-16-401-g001.jpg

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