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在小鼠中递送 SA35 和 SA40 肽可增强体液和细胞免疫应答,并赋予其抵抗微小隐孢子虫感染的保护作用。

Delivery of SA35 and SA40 peptides in mice enhances humoral and cellular immune responses and confers protection against Cryptosporidium parvum infection.

机构信息

European Union Reference Laboratory for Parasites, Istituto Superiore di Sanità, Rome, Italy.

出版信息

Parasit Vectors. 2019 May 15;12(1):233. doi: 10.1186/s13071-019-3486-8.

DOI:10.1186/s13071-019-3486-8
PMID:31092283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6518611/
Abstract

BACKGROUND

Cryptosporidium parvum is a major cause of diarrhea in children and ruminants at the earliest stages of life. Maternal antibodies represent the main shield of neonate mammals for most of the infections. Two recombinant antigens (SA35 and SA40), portions of two C. parvum proteins, were tested for their ability to induce immune responses in adult mice and for protection on neonate BALB/c mice born from females immunised by mucosal delivery of both peptides.

METHODS

Adult BALB/c mice were intraperitoneally immunised with SA35 and SA40, separately or mixed, and their immune response was characterised. Furthermore, BALB/c pregnant mice were immunised by mucosal delivery with an SA35/40 mix, before and during pregnancy. Soon after birth, their offspring were infected with two doses (1 × 10 and 5 × 10) of C. parvum oocysts and the parasitic burden was determined at 5 and 9 days post-infection.

RESULTS

Intraperitoneal immunisation with SA35 and SA40 induced specific IgG and IgG1 in serum, specific IgA in the intestinal mucosa, increase of CD3+/CD4+ and CD30+ cells in splenocytes, which produced IFN-γ. Neonates born from immunised mice and infected with 1 × 10 oocysts showed a significant reduction of oocysts and intestinal forms (23 and 42%, respectively). A reduction of all parasitic forms (96%; P < 0.05) was observed when neonates were infected with 5 × 10 oocysts.

CONCLUSIONS

SA35 and SA40 peptides induce specific humoral and cell-mediated immune responses to C. parvum in adult mice. Moreover, mucosal administration of the SA35/40 mix in pregnant mice reduces C. parvum burden in their litters.

摘要

背景

微小隐孢子虫是生命早期儿童和反刍动物腹泻的主要原因。母体抗体是大多数新生哺乳动物感染的主要保护屏障。两种重组抗原(SA35 和 SA40),两种微小隐孢子虫蛋白的部分,被测试其诱导成年小鼠免疫反应的能力,并对通过粘膜传递两种肽免疫的雌性所生的新生 BALB/c 小鼠进行保护。

方法

成年 BALB/c 小鼠分别或混合腹腔内免疫 SA35 和 SA40,并对其免疫反应进行了描述。此外,BALB/c 怀孕小鼠在怀孕前和怀孕期间通过粘膜输送进行 SA35/40 混合免疫。出生后不久,它们的后代用两剂(1×10 和 5×10)微小隐孢子虫卵囊感染,并在感染后 5 天和 9 天确定寄生虫负荷。

结果

SA35 和 SA40 腹腔内免疫诱导血清中特异性 IgG 和 IgG1,肠黏膜中特异性 IgA,脾细胞中 CD3+/CD4+和 CD30+细胞增加,产生 IFN-γ。从免疫小鼠中出生的新生儿并感染 1×10 卵囊,卵囊和肠型分别减少 23%和 42%。当新生儿感染 5×10 卵囊时,所有寄生虫形式(96%;P<0.05)均减少。

结论

SA35 和 SA40 肽在成年小鼠中诱导针对微小隐孢子虫的特异性体液和细胞介导免疫反应。此外,在怀孕的小鼠中粘膜给予 SA35/40 混合物可减少其后代的微小隐孢子虫负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/484750cf42e3/13071_2019_3486_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/856152c8935e/13071_2019_3486_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/f88bf5922e56/13071_2019_3486_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/ebff8561215a/13071_2019_3486_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/a12770c59d09/13071_2019_3486_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/d097d2c04903/13071_2019_3486_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/d19d554451f9/13071_2019_3486_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/c0d10131cd8b/13071_2019_3486_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/69fd6723c9d1/13071_2019_3486_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/484750cf42e3/13071_2019_3486_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/856152c8935e/13071_2019_3486_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/f88bf5922e56/13071_2019_3486_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/ebff8561215a/13071_2019_3486_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/a12770c59d09/13071_2019_3486_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/d097d2c04903/13071_2019_3486_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/d19d554451f9/13071_2019_3486_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/c0d10131cd8b/13071_2019_3486_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/69fd6723c9d1/13071_2019_3486_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42ab/6518611/484750cf42e3/13071_2019_3486_Fig9_HTML.jpg

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