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烟草花叶病毒样颗粒递送的自我扩增型人乳头瘤病毒 16 疫苗候选物。

A Self-Amplifying Human Papillomavirus 16 Vaccine Candidate Delivered by Tobacco Mosaic Virus-Like Particles.

机构信息

Aiiso Yufeng Li Family Department of Chemical and Nanoengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.

Shu and K. C. Chien and Peter Farrell Collaboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States.

出版信息

ACS Appl Bio Mater. 2024 Nov 18;7(11):7675-7683. doi: 10.1021/acsabm.4c01239. Epub 2024 Nov 8.

DOI:10.1021/acsabm.4c01239
PMID:39512153
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11648571/
Abstract

Virus-like particles (VLPs) are naturally occurring delivery platforms with potential for mRNA vaccines that can be used as an alternative to lipid nanoparticles. Here we describe a self-amplifying mRNA vaccine based on tobacco mosaic virus (TMV) expressing a mutated E7 protein from human papillomavirus 16 (HPV16). E7 is an early gene that plays a central role in viral replication and the oncogenic transformation of host cells, but nononcogenic mutant E7 proteins can suppress this activity. Immunization studies involving the delivery of self-amplifying mutant E7 mRNA packaged with TMV coat proteins confirmed the elicitation of E7-specific IgG antibodies. Additional splenocyte proliferation and cytokine profiling assays indicated the activation of humoral and cellular immune responses. We conclude that TMV particles are suitable for the delivery of mRNA vaccines and can preserve their integrity and functionality and .

摘要

病毒样颗粒（VLPs）是天然存在的递药平台，具有 mRNA 疫苗的潜力，可以作为脂质纳米粒的替代品。在这里，我们描述了一种基于烟草花叶病毒（TMV）的自扩增 mRNA 疫苗，该疫苗表达人乳头瘤病毒 16（HPV16）的突变 E7 蛋白。E7 是一种早期基因，在病毒复制和宿主细胞的致癌转化中发挥核心作用，但非致癌突变 E7 蛋白可以抑制这种活性。涉及用 TMV 衣壳蛋白包装的自扩增突变 E7 mRNA 进行免疫接种的研究证实了 E7 特异性 IgG 抗体的产生。额外的脾细胞增殖和细胞因子分析表明，体液和细胞免疫反应被激活。我们得出结论，TMV 颗粒适合于 mRNA 疫苗的递送，并能保持其完整性和功能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/3b337d2276c4/nihms-2040498-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/fc5ef87d8dc3/nihms-2040498-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/26a0888e219e/nihms-2040498-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/e2737bac2781/nihms-2040498-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/3b337d2276c4/nihms-2040498-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/fc5ef87d8dc3/nihms-2040498-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/26a0888e219e/nihms-2040498-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/e2737bac2781/nihms-2040498-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34dd/11648571/3b337d2276c4/nihms-2040498-f0005.jpg

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本文引用的文献

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mRNA-LNP vaccination-based immunotherapy augments CD8 T cell responses against HPV-positive oropharyngeal cancer.基于mRNA-LNP疫苗接种的免疫疗法增强了针对HPV阳性口咽癌的CD8 T细胞反应。
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mRNA vaccine in cancer therapy: Current advance and future outlook.mRNA 疫苗在癌症治疗中的应用：现状与展望。
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HPV16 E6/E7 -based mRNA vaccine is therapeutic in mice bearing aggressive HPV-positive lesions.HPV16 E6/E7 基于 mRNA 的疫苗对携带侵袭性 HPV 阳性病变的小鼠具有治疗作用。
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