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用亚马逊利什曼原虫的细胞外丝氨酸蛋白酶进行鼻内接种可使BALB/c小鼠获得针对感染的保护性免疫。

Intranasal vaccination with extracellular serine proteases of Leishmania amazonensis confers protective immunity to BALB/c mice against infection.

作者信息

de Matos Guedes Herbert Leonel, da Silva Costa Beatriz Lilian, Chaves Suzana Passos, de Oliveira Gomes Daniel Cláudio, Nosanchuk Joshua Daniel, De Simone Salvatore Giovanni, Rossi-Bergmann Bartira

机构信息

Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-902 Rio de Janeiro, RJ, Brazil.

出版信息

Parasit Vectors. 2014 Sep 19;7:448. doi: 10.1186/1756-3305-7-448.

DOI:10.1186/1756-3305-7-448
PMID:25239157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4261548/
Abstract

BACKGROUND

Previously, we demonstrated that unlike subcutaneous or intramuscular vaccination, intranasal vaccination of BALB/c mice with whole Leishmania amazonensis antigens leads to protection against cutaneous leishmaniasis. Here, the role of parasite serine proteases in the protective immunity was investigated.

FINDINGS

Serine Proteases were partially purified from both soluble (LaSP-Sol) and extracellular (LaSP-Ex) Leishmania amazonensis promastigote extracts by aprotinin-agarose chromatography. BALB/c mice were intranasally immunized with LaSP-Sol and LaSP-Ex prior to infection with L. amazonensis. LaSP-Ex but not LaSP-Sol vaccination led to significantly smaller lesions and parasite burdens as compared with non-vaccinated controls. Protection was accompanied by systemic Th1 polarization with increased IFN-γ and decreased IL-4 and IL-10 splenic production. Likewise, increased production of IFN-γ, IL-12 and IL-4 concomitant with decreased TGF-β and TNF-α was locally observed in the infected footpad.

CONCLUSION

This study indicates that extracellular serine proteases of L. amazonensis are strong candidates for a more defined intranasal vaccine against cutaneous leishmaniasis.

摘要

背景

此前，我们证明，与皮下或肌肉注射疫苗不同，用完整的亚马逊利什曼原虫抗原对BALB/c小鼠进行鼻内接种可预防皮肤利什曼病。在此，我们研究了寄生虫丝氨酸蛋白酶在保护性免疫中的作用。

研究结果

通过抑肽酶-琼脂糖层析从可溶性（LaSP-Sol）和细胞外（LaSP-Ex）亚马逊利什曼原虫前鞭毛体提取物中部分纯化丝氨酸蛋白酶。在感染亚马逊利什曼原虫之前，用LaSP-Sol和LaSP-Ex对BALB/c小鼠进行鼻内免疫。与未接种疫苗的对照组相比，接种LaSP-Ex而非LaSP-Sol可导致病变和寄生虫负荷显著减小。保护作用伴随着全身性Th1极化，脾脏中IFN-γ增加，IL-4和IL-10产生减少。同样，在感染的足垫中局部观察到IFN-γ、IL-12和IL-4产生增加，同时TGF-β和TNF-α减少。

结论

本研究表明，亚马逊利什曼原虫的细胞外丝氨酸蛋白酶是一种更明确的抗皮肤利什曼病鼻内疫苗的有力候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/56edbbf351c7/13071_2014_1619_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/c477a3f12541/13071_2014_1619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/be3a2c70547a/13071_2014_1619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/2ceb9bf7ff84/13071_2014_1619_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/56edbbf351c7/13071_2014_1619_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/c477a3f12541/13071_2014_1619_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/be3a2c70547a/13071_2014_1619_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/2ceb9bf7ff84/13071_2014_1619_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb19/4261548/56edbbf351c7/13071_2014_1619_Fig4_HTML.jpg

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