Institute of Plant Genetics, Polish Academy of Sciences, Strzeszyńska 34, 60-479 Poznań, Poland.
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, Wrocław, Poland.
Vaccine. 2018 Oct 1;36(41):6070-6076. doi: 10.1016/j.vaccine.2018.09.006. Epub 2018 Sep 7.
A formulation of a defined antigen dosage together with an appropriate and convenient immunisation regime are the main problems of a plant-derived oral vaccine against HBV. Both factors have to be mutually adjusted to ensure efficacious vaccination and to minimise the risk of oral tolerance acquisition. As based on previous research, solely oral immunisation appears to be of limited effectiveness, but a combined immunisation scheme via injection priming and oral boosting can be proposed. Thus, the previously optimised plant lyophilisate with accumulated S-HBsAg was orally administered in a series of mouse immunisation trials. The impact of various S-HBsAg oral dosages and concentrations on the induction of an active immune response was studied. Immunisation via i.m. priming followed by double oral boosting in 6-week intervals was comparably efficient as standard i.m. vaccination. Among the tested dosages, 2× 5 or 200 ng triggered effective and exclusively systemic responses. Mucosal adjuvants CTB or quillaja bark saponins as well as alhydrogel either had no or a negative effect on immune response, which indicates that a low-dosed plant lyophilisate as an oral booster vaccine may not require exogenous adjuvants. Additionally, a positive effect of S-HBsAg encapsulation in lyophilised cells on immune response stimulation was confirmed by comparison with the antigen released in the plant extract. The low-dosed plant lyophilisate with concentrated S-HBsAg was proven as an effective and convenient oral booster vaccine. Results of immunisation via a mixed injection-oral route provide the foundation for research on further standardisation of a plant-derived oral vaccine against HBV and details of immune response together with effects for health condition.
一种定义明确的抗原剂量配方与适当和方便的免疫方案是植物源性乙型肝炎口服疫苗的主要问题。这两个因素必须相互调整，以确保有效的免疫接种，并将口服耐受的风险降至最低。基于以前的研究，仅口服免疫似乎效果有限，但可以提出一种通过注射初免和口服加强的联合免疫方案。因此，之前优化的含有累积 S-HBsAg 的植物冻干物通过一系列小鼠免疫试验进行口服给药。研究了不同 S-HBsAg 口服剂量和浓度对主动免疫应答的诱导的影响。通过 i.m. 初免 followed 双 oral 加强在 6 周间隔的免疫与标准 i.m. 接种相当有效。在所测试的剂量中，2×5 或 200ng 触发了有效的、仅系统性的反应。粘膜佐剂 CTB 或 quillaja bark 皂素或 alhydrogel 要么没有影响，要么对免疫反应有负面影响，这表明作为口服加强疫苗的低剂量植物冻干物可能不需要外源性佐剂。此外，通过与植物提取物中释放的抗原进行比较，证实了 S-HBsAg 在冻干细胞中的包封对免疫应答刺激的积极影响。浓缩 S-HBsAg 的低剂量植物冻干物被证明是一种有效和方便的口服加强疫苗。通过混合注射-口服途径进行免疫的结果为进一步标准化植物源性乙型肝炎口服疫苗的研究提供了基础，并详细研究了免疫反应以及对健康状况的影响。
