División de Biología Molecular, IPICYT, Camino a la Presa San José 2055, 78216 San Luis Potosí, Mexico.
Plant Cell Rep. 2011 Mar;30(3):417-24. doi: 10.1007/s00299-010-0973-y. Epub 2010 Dec 25.
DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has been shown to be effective in humans. Nevertheless, dissatisfaction with the whole-cell preparations is due to the reactogenicity, which has to lead to the development of new safer formulations. Previously, we described the expression in tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis and tetanus exotoxins and two adjuvants. In this study, we examined whether the ingestion of tomato-derived sDPT protein induces specific antibodies in mice after three weekly doses scheme. A positive group immunized with DPT toxoids was included. Specific antibody levels were assessed in serum, gut and lung. Sera tested for IgG antibody response to pertussis, tetanus and diphtheria toxin showed responses to the foreign antigens; interestingly, the response to diphtheria epitope was similar to those observed in the positive group. We found higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in the tracheopulmonary fluid. High response of IgA against tetanus toxin was evident in gut, which was statistically comparable to that obtained in the positive group. The levels of response in these groups were higher than those in mice that received wild-type tomato. These findings support the concept of using transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine against diphtheria, pertussis, and tetanus.
DPT 疫苗旨在预防白喉、百日咳和破伤风,已被证明在人类中有效。然而,由于全细胞制剂的反应原性,人们对其并不满意,这促使人们开发新的更安全的制剂。此前,我们曾描述过在番茄中表达一种植物优化的合成基因,该基因编码含有白喉、百日咳和破伤风外毒素主要免疫保护表位的重组多肽 sDPT,以及两种佐剂。在这项研究中,我们研究了每周服用三次番茄来源的 sDPT 蛋白后,是否会在小鼠体内诱导特异性抗体。同时包括了一个用 DPT 类毒素免疫的阳性对照组。在血清、肠道和肺部评估特异性抗体水平。检测血清中针对百日咳、破伤风和白喉毒素的 IgG 抗体反应,结果显示对这些外来抗原产生了应答;有趣的是,对白喉表位的应答与阳性组观察到的应答相似。我们发现血清中的 IgG1 反应高于 IgG2a。在气管肺液中观察到适度的 IgG 应答。在肠道中,针对破伤风毒素的 IgA 高应答明显,与阳性组获得的应答在统计学上相当。这些组的应答水平高于接受野生型番茄的小鼠。这些发现支持使用表达 sDPT 多肽的转基因番茄作为白喉、百日咳和破伤风口服疫苗模型的概念。