Laboratório de Patologia de Moléstias Infecciosas, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Arch Dermatol Res. 2012 Jan;304(1):47-55. doi: 10.1007/s00403-011-1171-7. Epub 2011 Sep 1.
Leishmania (Viannia) shawi causes cutaneous lesions in humans. Parasite antigens conferring significant protection against American tegumentar leishmaniosis (ATL) might be important for the development of effective vaccine. Therefore, this work evaluates the protective effect of antigenic fractions released by L. shawi. Antigens released by promastigotes to culture medium were concentrated and isolated by SDS-PAGE. The three main fractions LsPass1 (>75 kDa), LsPass2 (75-50 kDa) and LsPass3 (<50 kDa) were electro-eluted according with their molecular mass. Immunized BALB/c mice were challenged with L. shawi promastigotes and the course of infection monitored during 5 weeks. LsPass1-challenged mice showed no protection, however, a strong degree of protection associated to smaller lesions and high expression of IFN-γ and TNF-α by CD4(+) T, CD8(+) T and double negative CD4CD8 cells was achieved in LsPass3-challenged mice. Furthermore, LsPass2-challenged mice showed an intermediated degree of protection associated to high levels of IFN-γ, IL-4 and IL-10 mRNA. In spite of increased expression of IFN-γ and TNF-α, high amounts of IL-4 and IL-10 mRNA were also detected in LsPass3-challenged mice indicating a possible contribution of these cytokines for the persistence of a residual number of parasites that may be important in inducing long-lasting immunity. Therefore, LsPass3 seems to be an interesting alternative that should be considered in the development of an effective vaccine against ATL.
沙氏利什曼原虫可引起人类皮肤损伤。对抗美洲皮肤利什曼病(ATL)具有重要保护作用的寄生虫抗原可能对开发有效疫苗至关重要。因此,本工作评估了沙氏利什曼原虫释放的抗原性片段的保护作用。用 SDS-PAGE 浓缩和分离从亲代虫体向培养基中释放的抗原。根据分子量,用电洗脱法从三个主要片段 LsPass1(>75 kDa)、LsPass2(75-50 kDa)和 LsPass3(<50 kDa)中分离。用 L. shawi 亲代虫体对免疫的 BALB/c 小鼠进行攻击,并在 5 周内监测感染过程。LsPass1 攻击的小鼠没有得到保护,但 LsPass3 攻击的小鼠表现出强烈的保护作用,病变较小,CD4+T、CD8+T 和双阴性 CD4CD8 细胞中 IFN-γ 和 TNF-α的高表达。此外,LsPass2 攻击的小鼠表现出中度保护作用,与高水平的 IFN-γ、IL-4 和 IL-10 mRNA 相关。尽管 IFN-γ 和 TNF-α的表达增加,但 LsPass3 攻击的小鼠也检测到大量的 IL-4 和 IL-10 mRNA,表明这些细胞因子可能有助于寄生虫数量的持续存在,这对诱导持久的免疫可能很重要。因此,LsPass3 似乎是一种有前途的选择,应在开发针对 ATL 的有效疫苗中加以考虑。