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重组YopE和LcrV候选疫苗可保护小鼠免受鼠疫和耶尔森氏菌病侵害。

Recombinant YopE and LcrV vaccine candidates protect mice against plague and yersiniosis.

作者信息

Gupta Ankit, Mahajan Pooja, Bhagyawant Sameer S, Saxena Nandita, Johri Atul Kumar, Kumar Subodh, Verma Shailendra Kumar

机构信息

Microbiology Division, Defence Research & Developmental Establishment, Jhansi Road, Gwalior, 474002, MP, India.

School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.

出版信息

Heliyon. 2024 May 18;10(10):e31446. doi: 10.1016/j.heliyon.2024.e31446. eCollection 2024 May 30.

Abstract

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1β from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with and . Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: , , and . However, the efficacy should be tested in other higher mammalian models.

摘要

目前尚无用于致命性鼠疫和耶尔森菌病的许可疫苗。因此,在小鼠模型中评估了重组YopE和LcrV抗原组合的疫苗潜力。与明矾混合的YopE和LcrV可引发强烈的体液免疫反应,其亚型分布倾向于IgG1和IgG2b亚类。还观察到,接种疫苗小鼠的脾细胞中IFN-γ、TNF-α、IL-6、IL-2和IL-1β的表达显著增强,以及YopE和LcrV特异性的IFN-γ诱导T细胞。YopE + LcrV制剂组合对100倍致死剂量感染提供了完全保护,而单独的LcrV和YopE分别提供了80%和60%的保护。同样,与单独给予YopE或LcrV的组相比,用YopE + LcrV接种的动物组在受到[具体病原体]攻击时,脾脏和血液中的菌落形成单位(CFU)计数显著更低。组织病理学证据强化了这些结果,表明YopE + LcrV制剂早在攻击后第3天就对急性肺损伤提供了更好的保护。总之,明矾佐剂的YopE + LcrV是一种有前景的疫苗制剂,可引发强烈的抗体反应,包括促炎细胞因子环境和T细胞效应功能,有助于对[具体病原体]感染产生保护性免疫。YopE和LcrV在所有三种人类致病性耶尔森菌物种中都保守,提供交叉保护。因此,我们目前的疫苗(YopE + LcrV)针对所有三种病原体:[具体病原体1]、[具体病原体2]和[具体病原体3]。然而,其疗效应在其他高等哺乳动物模型中进行测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a25/11141369/92cd9679b169/gr1.jpg

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