da Silva-Couto Luzinei, Ribeiro-Romão Raquel Peralva, Saavedra Andrea Franco, da Silva Costa Souza Beatriz Lilian, Moreira Otacílio Cruz, Gomes-Silva Adriano, Rossi-Bergmann Bartira, Da-Cruz Alda Maria, Pinto Eduardo Fonseca
Laboratório Interdisciplinar de Pesquisas Médicas - Instituto Oswaldo Cruz - FIOCRUZ, Rio de Janeiro, Brazil.
Laboratório de Imunofarmacologia - Instituto de Biofísica Carlos Chagas Filho, UFRJ, Rio de Janeiro, Brazil.
PLoS Negl Trop Dis. 2015 Jan 8;9(1):e3439. doi: 10.1371/journal.pntd.0003439. eCollection 2015 Jan.
Previous results have shown that oral and intranasal administration of particulate Leishmania (Leishmania) amazonensis antigens (LaAg) partially protects mice against L. amazonensis infection. However, vaccination studies on species of the subgenus Viannia, the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to-handle bio-models that accurately mimic the human disease. Recently, we demonstrated that the golden hamster is an appropriate model for studying the immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia) braziliensis. Using the golden hamster model, our current study investigated whether the protective effect of intranasal immunisation with LaAg can be extended to L. braziliensis infection.
METHODOLOGY/PRINCIPAL FINDINGS: Golden hamsters vaccinated with either two intranasal (IN) doses of LaAg (10 µg) or two intramuscular doses of LaAg (20 µg) were challenged 2 weeks post-vaccination with L. braziliensis. The results showed that IN immunisation with LaAg significantly reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At the experimental endpoint on day 114 post-infection, IN-immunised hamsters that were considered protected expressed IFN-γ and IL10 mRNA levels that returned to uninfected skin levels. In contrast to the nasal route, intramuscular (IM) immunisation failed to provide protection.
CONCLUSIONS/SIGNIFICANCE: These results demonstrate for the first time that the nasal route of immunisation can induce cross protection against L. braziliensis infection.
先前的研究结果表明,经口和经鼻给予利什曼原虫(亚马逊利什曼原虫)颗粒抗原(LaAg)可部分保护小鼠免受亚马逊利什曼原虫感染。然而,对在美洲引起皮肤和黏膜利什曼病的主要病原体维安亚亚属物种进行疫苗接种研究时,由于缺乏能准确模拟人类疾病的易于操作的生物模型而受到阻碍。最近,我们证明金黄仓鼠是研究巴西利什曼原虫(维安亚利什曼原虫)引起的皮肤利什曼病免疫发病机制的合适模型。利用金黄仓鼠模型,我们当前的研究调查了经鼻免疫LaAg的保护作用是否能扩展到巴西利什曼原虫感染。
方法/主要发现:用两剂经鼻(IN)LaAg(10μg)或两剂肌肉注射LaAg(20μg)对金黄仓鼠进行疫苗接种,接种后2周用巴西利什曼原虫进行攻击。结果表明,经鼻免疫LaAg可显著减少病变生长和寄生虫负荷以及血清IgG和IgG2水平。在感染后第114天的实验终点,被认为受到保护的经鼻免疫仓鼠表达的IFN-γ和IL10 mRNA水平恢复到未感染皮肤的水平。与经鼻途径相反,肌肉注射(IM)免疫未能提供保护。
结论/意义:这些结果首次证明经鼻免疫途径可诱导对巴西利什曼原虫感染的交叉保护。