中文摘要：由于利什曼病是由致病性和毒力不同的利什曼原虫引起的，因此抗原制剂是利什曼病诊断和疫苗接种成功的主要特征。理想情况下，这些抗原可由不同的抗体识别，并对绝大多数利什曼原虫都具有免疫原性。为此，本研究选择了六种潜在的免疫原性肽，其来自噬菌体展示或斑点合成的利什曼原虫组蛋白和膜分子，并将其包埋在脂质体结构中。本研究用这些多肽免疫新西兰兔，并测定嵌合抗原的免疫原性。研究发现，这些多肽用于巴西利什曼原虫或婴儿利什曼原虫的体液免疫，诱导产生了抗体。为了评估诱导细胞活化的先天性反应，用巴西利什曼原虫或婴儿利什曼原虫体外感染多肽混合免疫兔的巨噬细胞，研究发现多肽组合产生了ifn – γ、IL-12、IL-4和tgf - β，引起了Th1和Th2细胞免疫反应，也诱导了iNOS的高表达。可见由组蛋白和寄生虫膜分子组成的多肽能够模拟寄生虫蛋白，诱导对CD4+T细胞Th1和Th2分化起重要作用的细胞因子和效应分子来控制寄生虫感染。最后，该肽诱导了免疫平衡，这对预防免疫病理紊乱、炎症反应和控制寄生虫感染非常重要。
外文摘要：Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptide mix generated the IFN-gamma, IL-12, IL-4 and TGF-beta that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.
外文关键词：mimetic peptides; cytokines; in vitro infection; vaccines; leishmaniasis
作者：Guedes, DC；Santiani, MH；Carvalho, J；Soccol, CR；Minozzo, JC；de Avila, RAM；de Moura, JF；Ramos, ELP；Castro, GR；Chavez-Olortegi, C；Thomaz-Soccol, V
作者单位：Univ Fed Parana；Secretaria Saude Estado Parana；Univ Extremo Sul Catarinense；Univ Nacl La Plata UNLP；Univ Nacl Rosario；Univ Fed Minas Gerais
期刊名称：FRONTIERS IN CHEMISTRY
期刊影响因子：3.693
出版年份：2021
出版刊次：8
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