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首页> 外文期刊>Vaccine >Immunostimulatory oligodeoxynucleotides are potent enhancers of protective immunity in mice immunized with recombinant ORFF leishmanial antigen
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Immunostimulatory oligodeoxynucleotides are potent enhancers of protective immunity in mice immunized with recombinant ORFF leishmanial antigen

机译：免疫刺激性寡聚脱氧核苷酸是用重组ORFF利什曼抗原免疫的小鼠中保护性免疫的有效增强剂

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摘要

Unmethylated CpG dinucleotides in bacterial DNA or synthetic oligonucleotides (ODN) have proved as promising adjuvants for promotion of T helper 1 (Th1) type immune response. The potent Th1 like immune activation by CpG-ODNs suggests a possible utility for vaccination against leishmaniasis. We therefore investigated the effect of ODN containing immunostimulatory CG motifs as adjuvant with recombinant ORFF (rORFF) leishmanial antigen. BALB/c mice were vaccinated with the rORFF with or without CpG-ODN as adjuvant and then challenged with Leishmania donovani metacyclic promastigotes. Administration of CpG-ODN alone resulted in partial protection against challenge with L. donovani in BALB/c mice. Combination of rORFF and CpG-ODN showed enhanced reduction in parasite load (84%) when compared to rORFF (56%) vaccinated mice. Immunization with rORFF alone did not induce the typical Th response whereas co-administration of rORFF with CpG-ODN resulted in enhanced production of immunoglobulin G2a and interferon gamma. Our results further demonstrate that CpG-ODN alone or in combination with rORFF resulted in a dose dependent increase of nitric oxide production in activated macrophages. These studies suggest that CpG-ODN are promising immune enhancers for vaccination against visceral leishmaniasis.
机译：细菌DNA或合成寡核苷酸（ODN）中的未甲基化CpG二核苷酸已被证明是促进T辅助1（Th1）型免疫应答的有前途的佐剂。类似CpG-ODN的有效Th1免疫激活表明，针对利什曼病的疫苗接种可能具有实用性。因此，我们研究了含有免疫刺激性CG主题的ODN作为重组ORFF（rORFF）利什曼抗原的佐剂的作用。用rORFF接种或不接种CpG-ODN的佐剂对BALB / c小鼠进行疫苗接种，然后用利什曼原虫donovani继发性前鞭毛体攻击。单独施用CpG-ODN可以部分保护BALB / c小鼠免受多诺氏乳杆菌的攻击。与rORFF（56％）疫苗接种的小鼠相比，rORFF和CpG-ODN的组合显示出增加的寄生虫载量降低（84％）。单独用rORFF免疫不会引起典型的Th反应，而将rORFF与CpG-ODN并用可提高免疫球蛋白G2a和干扰素γ的产生。我们的结果进一步证明，单独的CpG-ODN或与rORFF联合使用会导致激活的巨噬细胞中一氧化氮生成的剂量依赖性增加。这些研究表明，CpG-ODN是有希望的针对内脏利什曼病的免疫增强剂。

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