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恒河猴中灭活轮状病毒的免疫原性,及免疫机制的评估。

Immunogenicity of inactivated rotavirus in rhesus monkey, and assessment of immunologic mechanisms.

机构信息

Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on severe Infectious Disease, Kunming, China.

出版信息

Hum Vaccin Immunother. 2023 Dec 31;19(1):2189598. doi: 10.1080/21645515.2023.2189598. Epub 2023 Mar 30.

DOI:10.1080/21645515.2023.2189598
PMID:36994772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10088923/
Abstract

Rotavirus is one of the main pathogens causing severe diarrhea in infants and young children < 5 years of age. The development of the next-generation rotavirus vaccine is of great significance for preventing rotavirus infection and reducing severe mortality. The current study aimed to develop and evaluate the immunogenicity of inactivated rotavirus vaccine (IRV) in rhesus monkeys. Monkeys received two or three IRV injections intramuscularly at a 4-week interval. Neutralizing antibodies, cellular immunity, PBMC gene expression profiling, and immune persistence were evaluated. Three-dose immunization of IRV induced a higher level of neutralizing, IgG and IgA antibodies compared to two-dose immunization. IRV induced IFN-γ secretion to mediate cellular immune responses, including robust pro-inflammatory and antiviral responses. Chemokine-mediated signaling pathways and immune response were broadly activated by IRV injection. The IRV-induced neutralizing antibodies resulting from two doses returned to baseline levels 20 weeks after full immunization, while those resulting from three doses returned to baseline levels 44 weeks after full immunization. Increasing immunization dose and injection number will help to improve IRV immunogenicity and neutralizing antibody persistence.

摘要

轮状病毒是导致 5 岁以下婴幼儿严重腹泻的主要病原体之一。开发下一代轮状病毒疫苗对于预防轮状病毒感染和降低严重死亡率具有重要意义。本研究旨在开发和评估猕猴体内灭活轮状病毒疫苗(IRV)的免疫原性。猴子每隔 4 周肌肉注射两次或三次 IRV。评估中和抗体、细胞免疫、PBMC 基因表达谱和免疫持久性。与两剂免疫相比,三剂 IRV 免疫诱导更高水平的中和、IgG 和 IgA 抗体。IRV 诱导 IFN-γ 分泌来介导细胞免疫反应,包括强烈的促炎和抗病毒反应。IRV 注射广泛激活趋化因子介导的信号通路和免疫反应。两剂 IRV 诱导的中和抗体在完全免疫后 20 周恢复到基线水平,而三剂 IRV 诱导的中和抗体在完全免疫后 44 周恢复到基线水平。增加免疫剂量和注射次数有助于提高 IRV 的免疫原性和中和抗体持久性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/8ed796da8420/KHVI_A_2189598_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/a375d5969e40/KHVI_A_2189598_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/863aad764d4a/KHVI_A_2189598_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/713351ee7e54/KHVI_A_2189598_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/f014370180b4/KHVI_A_2189598_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/de09cf75ced2/KHVI_A_2189598_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/6c6ed1c29efb/KHVI_A_2189598_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/8ed796da8420/KHVI_A_2189598_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/a375d5969e40/KHVI_A_2189598_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/863aad764d4a/KHVI_A_2189598_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/713351ee7e54/KHVI_A_2189598_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/f014370180b4/KHVI_A_2189598_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/de09cf75ced2/KHVI_A_2189598_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/6c6ed1c29efb/KHVI_A_2189598_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a80/10088923/8ed796da8420/KHVI_A_2189598_F0007_OC.jpg

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