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突变型CM-pGP3S作为一种新型减毒活直肠疫苗可预防生殖道感染。

mutant CM-pGP3S as a novel attenuated live rectal vaccine protects against genital tract infection.

作者信息

Ma Jingyue, Zhang Tianyuan, Tian Qi, Xiao Meng, Han Long, Liu Quanzhong, Zhong Guangming, Liu Yuanjun

机构信息

Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, China.

Shanghai Institute of Virology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Cell Infect Microbiol. 2025 May 13;15:1550455. doi: 10.3389/fcimb.2025.1550455. eCollection 2025.

DOI:10.3389/fcimb.2025.1550455
PMID:40433661
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12106443/
Abstract

INTRODUCTION

(CT) is a major sexually transmitted pathogen with severe complications. Using (CM) as a model, this study evaluates the attenuated mutant (CM-pGP3S) as a novel rectal vaccine to protect against genital tract infection and pathology.

METHODS

Female C57BL/6 mice were rectally immunized with low (1×10), middle (1×10), or high (1×10) doses of CM-pGP3S. Mice were challenged intravaginally with wild-type 63 days post-immunization. Protection was assessed via genital shedding, hydrosalpinx incidence (gross/histopathology), serum IgG, fecal IgA, and T cell responses. Gut microbiota stability was analyzed using qPCR.

RESULTS

CM-pGP3S immunization significantly reduced CM-WT genital shedding duration (3-7 days vs. 21 days in controls, < 0.01) and hydrosalpinx incidence (0% vs. 80% in controls, < 0.01). Elevated systemic and mucosal immunity were observed, including higher serum IgG (1:100-1:1600 dilutions,  < 0.05-0.01) and fecal IgA ( < 0.05-0.01). CD4 and CD8 T cells exhibited increased IFN-γ ( < 0.01), while CD8 T cells showed elevated TNF-α and IL-2 ( < 0.05). No colitis or significant gut microbiota disruption occurred post-immunization.

DISCUSSION

Rectal CM-pGP3S vaccination induces robust transmucosal immunity, protecting against genital infection and pathology without gastrointestinal adverse effects. This highlights its potential as a safe and effective mucosal vaccine strategy to combat CT genital tract infections.

摘要

引言

沙眼衣原体(CT)是一种主要的性传播病原体,可导致严重并发症。本研究以沙眼衣原体小鼠模型(CM)为模型,评估减毒突变体沙眼衣原体(CM-pGP3S)作为一种新型直肠疫苗预防生殖道感染及病变的效果。

方法

将低(1×10)、中(1×10)或高(1×10)剂量的CM-pGP3S经直肠免疫雌性C57BL/6小鼠。免疫63天后,经阴道用野生型沙眼衣原体攻击小鼠。通过生殖道衣原体脱落情况、输卵管积水发生率(大体/组织病理学)、血清IgG、粪便IgA和T细胞反应评估疫苗的保护效果。采用qPCR分析肠道微生物群稳定性。

结果

CM-pGP3S免疫显著缩短了沙眼衣原体野生型(CM-WT)在生殖道的脱落持续时间(对照组为21天,免疫组为3 - 7天,P<0.01),降低了输卵管积水发生率(对照组为80%,免疫组为0%,P<0.01)。观察到全身和黏膜免疫增强,包括更高的血清IgG(1:100 - 1:1600稀释度,P<0.05 - 0.01)和粪便IgA(P<0.05 - 0.01)。CD4和CD8 T细胞产生的IFN-γ增加(P<0.01),而CD8 T细胞产生的TNF-α和IL-2升高(P<0.05)。免疫后未发生结肠炎或明显的肠道微生物群破坏。

讨论

直肠接种CM-pGP3S疫苗可诱导强大的跨黏膜免疫,预防生殖道衣原体感染及病变,且无胃肠道不良反应。这突出了其作为一种安全有效的黏膜疫苗策略对抗CT生殖道感染的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/8d8bea2a89fe/fcimb-15-1550455-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/6dc98d171e87/fcimb-15-1550455-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/214f3c8284e2/fcimb-15-1550455-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/0ccf57ba5313/fcimb-15-1550455-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/8d8bea2a89fe/fcimb-15-1550455-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/6dc98d171e87/fcimb-15-1550455-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/214f3c8284e2/fcimb-15-1550455-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/0ccf57ba5313/fcimb-15-1550455-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb2/12106443/8d8bea2a89fe/fcimb-15-1550455-g004.jpg

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