Agnello Davide, Hervé Christine A, Lavaux Amandine, Darniot Magali, Guillon Patrice, Charpilienne Annie, Pothier Pierre
Laboratoire de Virologie et Centre National de Référence des Virus Entériques, CHU et Faculté de Médecine, Université de Bourgogne, 7 boulevard Jeanne d'Arc, 21079 Dijon Cedex, France.
J Virol. 2006 Apr;80(8):3823-32. doi: 10.1128/JVI.80.8.3823-3832.2006.
Rotavirus (RV) is the main etiological agent of severe gastroenteritis in infants, and vaccination seems the most effective way to control the disease. Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when administered by the intranasal (i.n.) route. In this study, we show that administration of 2/6-VLPs by the intrarectal (i.r.) route together with either cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant protects adult mice against RV infection. Moreover, when CT is used, RV shedding in animals immunized by the i.r. route is even reduced in comparison with that in animals immunized by the i.n. route. Humoral and cellular immune responses induced by these immunization protocols were analyzed. We found that although i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG) and IgA levels in serum, intestinal anti-RV IgA production is higher in mice immunized by the i.r. route. Cellular immune response has been evaluated by measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display higher gamma interferon production in spleen and PPs, respectively. In conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against RV infection in mice and is more efficient than i.n. immunization in inducing an anti-RV immune response in intestinal mucosa.
轮状病毒(RV)是婴儿严重胃肠炎的主要病原体,接种疫苗似乎是控制该疾病的最有效方法。据报道,由病毒蛋白6(VP6)和VP2组成的重组轮状病毒样颗粒(2/6-VLPs)经鼻内(i.n.)途径给药时可在小鼠中诱导保护性免疫。在本研究中,我们发现经直肠(i.r.)途径给予2/6-VLPs并联合霍乱毒素(CT)或含CpG的寡脱氧核苷酸作为佐剂,可保护成年小鼠免受RV感染。此外,当使用CT时,与经鼻内途径免疫的动物相比,经直肠途径免疫的动物体内RV排泄量甚至更低。我们分析了这些免疫方案诱导的体液和细胞免疫反应。我们发现,虽然经直肠免疫2/6-VLPs诱导的血清中RV特异性免疫球蛋白G(IgG)和IgA水平较低,但经直肠途径免疫的小鼠肠道抗RV IgA产生量更高。通过用RV体外再刺激后测量脾脏和派尔集合淋巴结细胞(PPs)产生的细胞因子来评估细胞免疫反应。经鼻内和经直肠途径免疫的小鼠分别在脾脏和PPs中表现出更高的γ干扰素产生量。总之,我们证明经直肠免疫2/6-VLPs可保护小鼠免受RV感染,并且在诱导肠道黏膜抗RV免疫反应方面比经鼻内免疫更有效。