Ma Jingyue, Zhang Tianyuan, Tian Qi, Xiao Meng, Han Long, Liu Quanzhong, Zhong Guangming, Liu Yuanjun
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.
Front Cell Infect Microbiol. 2025 May 13;15:1550455. doi: 10.3389/fcimb.2025.1550455. eCollection 2025.
(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.
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.
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.
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.
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。
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。
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。
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。