Diniz S N, Reis B S, Goes T S, Zouain C S, Leite M F, Goes A M
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Caixa Postal 486, CEP 32270-901, Belo Horizonte, MG, Brazil.
Vaccine. 2004 Jan 2;22(3-4):485-92. doi: 10.1016/j.vaccine.2003.07.017.
Paracoccidioides brasiliensis causes a chronic granulomatous mycosis prevalent in South America, and cell-mediated immunity represents the principal mode of protection against this fungal infection. We investigated whether immunization with P. brasiliensis antigens fractionated by anionic chromatography on fast protein liquid chromatography (FPLC) could elicit protective immunity. BALB/c mice were immunized by subcutaneous injection of either 10 microg fractions 0 (F0), II (FII) or III (FIII) in the presence of 100 microg of Corynebacterium parvum and 1 mg of Al(OH)(3) and challenged with pathogenic P. brasiliensis strain. Mice immunized with F0 presented cellular and humoral immune responses with significant production of IFN-gamma, and high levels of IgG2a and IgG3 isotypes. Immunization with FII induced significant production of IFN-gamma and IL-10 associated with high levels of IgG1 and IgG2a. It was demonstrated that immunization with F0 or FII promoted significant decrease of organ colony-forming units (CFUs) in the lung after challenge infection without fungi dissemination to the spleen or liver. In contrast, FIII immunized mice develop a progressive disseminated disease to spleen and liver presented significant levels of INF-gamma, IL-10 or TGF-beta associated with high production of IgG1 and IgG2a with low production of IgG2b and IgG3 after challenge infection. Taken together, these findings suggest that antigens of F0 and FII are reliable vaccine candidates against the paracoccidioidomycosis.
巴西副球孢子菌可引发一种在南美洲流行的慢性肉芽肿性真菌病，细胞介导的免疫是抵御这种真菌感染的主要保护方式。我们研究了通过快速蛋白质液相色谱（FPLC）上的阴离子色谱法分离的巴西副球孢子菌抗原进行免疫是否能引发保护性免疫。将BALB/c小鼠在存在100微克微小棒状杆菌和1毫克氢氧化铝的情况下，皮下注射10微克的0号组分（F0）、II号组分（FII）或III号组分（FIII）进行免疫，然后用致病性巴西副球孢子菌菌株进行攻击。用F0免疫的小鼠呈现出细胞和体液免疫反应，显著产生干扰素-γ，以及高水平的IgG2a和IgG3亚型。用FII免疫诱导显著产生与高水平IgG1和IgG2a相关的干扰素-γ和白细胞介素-10。结果表明，用F0或FII免疫可在攻击感染后促进肺部器官集落形成单位（CFU）显著减少，且真菌不会扩散至脾脏或肝脏。相比之下，用FIII免疫的小鼠发展为向脾脏和肝脏的进行性播散性疾病，在攻击感染后呈现出显著水平的干扰素-γ、白细胞介素-10或转化生长因子-β，与高水平的IgG1和IgG2a产生相关，而IgG2b和IgG3产生较低。综上所述，这些发现表明F0和FII的抗原是抗副球孢子菌病的可靠候选疫苗。
