Ramírez Laura, Iborra Salvador, Cortés Jimena, Bonay Pedro, Alonso Carlos, Barral-Netto Manoel, Soto Manuel
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, (CSIC-UAM), Universidad Autónoma de Madrid, 28049 Madrid, Spain.
J Biomed Biotechnol. 2010;2010:181690. doi: 10.1155/2010/181690. Epub 2010 Jan 26.
Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-gamma in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity.
利什曼病是一个日益严重的公共卫生问题,目前尚无有效的疫苗。我们之前已经证明,用核糖体蛋白提取物与CpG寡脱氧核苷酸联合给药进行疫苗接种,可保护易感的BALB/c小鼠免受原发性硕大利什曼原虫感染。在此,我们评估这种疫苗赋予的对二次感染的长期免疫力。我们发现,接种疫苗并感染的BALB/c小鼠能够控制继发性硕大利什曼原虫的攻击,因为在再感染部位未观察到炎症,且寄生虫数量极少。此外,虽然在原发性感染部位的引流淋巴结中观察到寄生虫负荷增加,但我们在该部位未检测到炎症病变。对再感染的抵抗力与针对寄生虫抗原的主要Th1反应相关。因此,从二次感染部位的脾脏和引流淋巴结建立的细胞培养物在不产生IL-4和IL-10细胞因子的情况下产生高水平的寄生虫特异性IFN-γ。此外,再次感染的小鼠抗利什曼原虫抗体的IgG2a/IgG1比值较高。我们的结果表明,在初次攻击中预防病理的核糖体疫苗与寄生虫持续存在相结合,可能对长期维持免疫力有效。