Heinimäki Suvi, Tamminen Kirsi, Hytönen Vesa P, Malm Maria, Blazevic Vesna
Vaccine Development and Immunology/Vaccine Research Center, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Protein Dynamics group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Vaccines (Basel). 2020 Jul 7;8(3):365. doi: 10.3390/vaccines8030365.
Novel adjuvants present a concern for adverse effects, generating a need for alternatives. Rotavirus inner capsid VP6 protein could be considered a potential candidate, due to its ability to self-assemble into highly immunogenic nanospheres and nanotubes. These nanostructures exhibit immunostimulatory properties, which resemble those of traditional adjuvants, promoting the uptake and immunogenicity of the co-administered antigens. We have previously elucidated an adjuvant effect of VP6 on co-delivered norovirus and coxsackievirus B1 virus-like particles, increasing humoral and cellular responses and sparing the dose of co-delivered antigens. This study explored an immunostimulatory effect of VP6 nanospheres on smaller antigens, P particles formed by protruding domain of a norovirus capsid protein and a short peptide, extracellular matrix protein (M2e) of influenza A virus. VP6 exhibited a notable improving impact on immune responses induced by P particles in immunized mice, including systemic and mucosal antibody and T cell responses. The adjuvant effect of VP6 nanospheres was comparable to the effect of alum, except for induction of superior mucosal and T cell responses when P particles were co-administered with VP6. However, unlike alum, VP6 did not influence M2e-specific immune responses, suggesting that the adjuvant effect of VP6 is dependent on the particulate nature of the co-administered antigen.
新型佐剂存在不良反应问题，因此需要寻找替代物。轮状病毒内衣壳VP6蛋白可被视为一个潜在候选物，因其能够自组装成高度免疫原性的纳米球和纳米管。这些纳米结构具有免疫刺激特性，类似于传统佐剂，可促进共同给药抗原的摄取和免疫原性。我们之前已阐明VP6对共同递送的诺如病毒和柯萨奇病毒B1病毒样颗粒的佐剂作用，可增强体液和细胞反应，并节省共同递送抗原的剂量。本研究探讨了VP6纳米球对较小抗原的免疫刺激作用，这些抗原包括由诺如病毒衣壳蛋白突出结构域形成的P颗粒以及甲型流感病毒的短肽细胞外基质蛋白（M2e）。VP6对免疫小鼠中P颗粒诱导的免疫反应有显著改善作用，包括全身和黏膜抗体以及T细胞反应。VP6纳米球的佐剂作用与明矾相当，不过当P颗粒与VP6共同给药时，VP6诱导的黏膜和T细胞反应更优。然而，与明矾不同的是，VP6不影响M2e特异性免疫反应，这表明VP6的佐剂作用取决于共同给药抗原的颗粒性质。
