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接种无效突变体可诱导BALB/c小鼠产生针对感染的长期保护作用。

Inoculation of the Null Mutant Induces Long-Term Protection against Infection in BALB/c Mice.

作者信息

Soto Manuel, Ramírez Laura, Solana José Carlos, Cook Emma C L, Hernández-García Elena, Requena José María, Iborra Salvador

机构信息

Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Departamento de Biología Molecular, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

WHO Collaborating Centre for Leishmaniasis, National Centre for Microbiology, Instituto de Salud Carlos III, 28220 Madrid, Spain.

出版信息

Microorganisms. 2021 Feb 12;9(2):363. doi: 10.3390/microorganisms9020363.

DOI:10.3390/microorganisms9020363
PMID:33673117
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7918614/
Abstract

parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to challenge due to their inability to mount parasite-dependent IFN-γ-mediated responses. Here, we analyzed the capacity of a single administration of the genetically-modified attenuated line in preventing cutaneous leishmaniasis in mice challenged with virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to Old World species. Vaccinated mice showed a reduction in the disease evolution due to challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti- IgG2a circulating antibodies accompanied to the induction of -driven specific IFN-γ systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-ϒ production by CD4 and CD8 T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate as a candidate for the development of human vaccines.

摘要

寄生虫是新世界皮肤利什曼病的病原体。BALB/c小鼠由于无法产生依赖寄生虫的IFN-γ介导的反应,对感染高度敏感。在此,我们分析了单次给予基因改造减毒株预防感染强毒寄生虫小鼠皮肤利什曼病的能力。在先前的研究中,这种减毒活疫苗已证明可诱导针对旧世界物种引起的鼠利什曼病的长期保护。接种疫苗的小鼠因感染而导致的疾病进展有所减轻,即皮肤病变和寄生虫负荷减少。与对照动物相比,感染后,受保护的小鼠显示出循环抗IgG2a抗体,并伴有诱导的依赖寄生虫的特异性IFN-γ全身反应。在感染部位引流淋巴结进行的分析显示,CD4和CD8 T细胞产生的寄生虫特异性IFN-γ增加,针对利什曼原虫抗原的IL-10分泌减少。由于接种这种活疫苗所产生的免疫可对不同形式的鼠利什曼病产生保护作用,我们假定其可作为人类疫苗开发的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/b54e39a2963c/microorganisms-09-00363-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/cb4cb3c68989/microorganisms-09-00363-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/bc67bca774c6/microorganisms-09-00363-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/28160cbfe045/microorganisms-09-00363-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/0f56e9cda6b5/microorganisms-09-00363-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/b54e39a2963c/microorganisms-09-00363-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/cb4cb3c68989/microorganisms-09-00363-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/bc67bca774c6/microorganisms-09-00363-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/28160cbfe045/microorganisms-09-00363-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/0f56e9cda6b5/microorganisms-09-00363-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3432/7918614/b54e39a2963c/microorganisms-09-00363-g005.jpg

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Subcutaneous Immunization of Null Mutant Line Reduces the Severity of the Experimental Visceral Leishmaniasis in BALB/c Mice.对基因敲除突变系进行皮下免疫可减轻BALB/c小鼠实验性内脏利什曼病的严重程度。
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