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在实验性皮肤利什曼病模型中评估含亚马逊利什曼原虫膜抗原制剂的疫苗效力。

Evaluation of vaccinal effectiveness of preparations containing membrane antigens of Leishmania (L.) amazonensis in experimental cutaneous leishmaniasis model.

作者信息

Ribeiro João G, Ferreira Amália S, Macedo Sharon R A, Rossi Norton R D L P, da Silva Mayara C P, Guerra Rosane N M, de Barros Neuza B, Nicolete Roberto

机构信息

Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), Porto Velho, RO, Brazil; Instituto Federal do Amazonas (IFAM), Campus Humaitá, Humaitá-AM, Brazil.

Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz (Fiocruz Rondônia), Porto Velho, RO, Brazil.

出版信息

Int Immunopharmacol. 2017 Jun;47:227-230. doi: 10.1016/j.intimp.2017.04.014. Epub 2017 Apr 25.

Abstract

American tegumentary leishmaniasis (ATL) is considered a neglected disease, for which an effective vaccine or an efficient diagnosis is not yet available and whose chemotherapeutic arsenal is threatened by the emergence of resistance by etiological agents such as Leishmania amazonensis. ATL is endemic in poor countries and has a high incidence in Brazil. Vaccines developed from native parasite fractions have led to the identification of defined antigenic subunits and the development of vaccine adjuvant technology. The purpose of the present study was to develop and compare preparations based on membrane antigens from L. amazonensis, as a biotechnological prototype for the immunoprophylaxis of the disease in a murine experimental model. For this purpose, batches of biodegradable polymeric micro/nanoparticles were produced, characterized and compared with other parasite's antigens in solution. All preparations containing membrane antigens presented low toxicity on murine macrophages. The in vivo evaluation of immunization efficacy was performed against a challenge with L. amazonensis, along with an evaluation of the immune response profile generated in BALB/C mice. The animals were followed for sample processing and quantification of serum-specific cytokines, nitrites and antibodies. The sera of animals immunized with the non-encapsulated antigen formulations showed higher intensities of nitrites and total IgGs. This approach evidenced the importance of the biological studies involving the immune response of the host against the parasite being interconnected and related to the subfractionation of its proteins in the search for more effective vaccine candidates.

摘要

美洲皮肤利什曼病(ATL)被视为一种被忽视的疾病,目前尚无有效的疫苗或高效的诊断方法,而且其化疗药物库正受到诸如亚马逊利什曼原虫等病原体耐药性出现的威胁。ATL在贫穷国家呈地方性流行,在巴西发病率很高。从天然寄生虫组分开发的疫苗已促使确定了明确的抗原亚基,并推动了疫苗佐剂技术的发展。本研究的目的是开发并比较基于亚马逊利什曼原虫膜抗原的制剂,作为在小鼠实验模型中对该疾病进行免疫预防的生物技术原型。为此,制备了几批可生物降解的聚合物微/纳米颗粒,对其进行了表征,并与溶液中的其他寄生虫抗原进行了比较。所有含有膜抗原的制剂对小鼠巨噬细胞的毒性都很低。针对亚马逊利什曼原虫攻击进行了免疫效力的体内评估,同时还评估了在BALB/C小鼠中产生的免疫反应谱。对动物进行跟踪以便进行样本处理以及血清特异性细胞因子、亚硝酸盐和抗体的定量分析。用未封装抗原制剂免疫的动物血清中亚硝酸盐和总IgG的强度更高。这种方法证明了涉及宿主对寄生虫免疫反应的生物学研究的重要性,这些研究相互关联,并且与在寻找更有效的候选疫苗过程中对寄生虫蛋白质进行亚分级有关。

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