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Modular virus-like particles for sublingual vaccination against group A streptococcus

机译：用于舌下接种A组链球菌的模块化病毒样颗粒

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Infection with Group A streptococcus (GAS) an oropharyngeal pathogen leads to mortality and morbidity, primarily among developing countries and indigenous populations in developed countries. The development of safe and affordable GAS vaccines is challenging, due to the presence of various unique GAS serotypes, antigenic variation within the same serotype, and potential auto-immune responses. In the present study, we evaluated the use of a sublingual freeze-dried (FD) formulation based on immunogenic modular virus-like particles (VLPs) carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS vaccine for inducing protective systemic and mucosal immunity. By using in vivo tracing of the sublingual J8-VLPs, we visualized the draining of J8-VLPs into the submandibular lymph nodes, in parallel with its rapid absorption into the systemic circulation, which support the induction of effective immune responses in both systemic and mucosa! compartments. The sublingual administration of J8-VLPs resulted in a high serum IgG antibody level, with a good balance of Thi and Th2 immune responses. Of note, sublingual vaccination with J8-VLPs elicited high levels of IgA antibody in the saliva. The co-administration of mucosal adjuvant cholera toxin (CT) further enhanced the increase in salivary IgA antibody levels induced by the J8-VLPs formulation. Moreover, the levels of salivary IgA and serum IgG observed following the administration of the CT-adjuvanted FD formulation of J8-VLPs (FD-J8-VLPs) and non-FD formulation of J8-VLPs were comparable. In fact, the saliva isolated from mice immunized with J8-VLPs and FD-J8-VLPs with CT demonstrated opsonizing activity against GAS in vitro. Thus, we observed that the sublingually delivered FD formulation of microbially produced modular VLPs could prevent and control GAS diseases in endemic areas in a cost-effective manner. (C) 2016 Elsevier Ltd. All rights reserved.
机译：口咽病原体感染A组链球菌（GAS）会导致死亡和发病，主要是在发展中国家和发达国家的土著人群中。由于存在多种独特的GAS血清型，同一血清型内的抗原变异以及潜在的自身免疫反应，因此开发安全，负担得起的GAS疫苗具有挑战性。在本研究中，我们评估了基于携带J8肽（J8-VLPs）的免疫原性模块化病毒样颗粒（VLP）的舌下冷冻干燥（FD）制剂的使用，作为一种潜在的安全且经济高效的GAS疫苗诱导保护性全身和粘膜免疫。通过使用舌下J8-VLP的体内追踪，我们观察到J8-VLPs排入下颌下淋巴结，同时其迅速吸收到全身循环中，这支持在全身和粘膜中诱导有效的免疫反应！隔间。 J8-VLP的舌下给药导致高血清IgG抗体水平，并具有Thi和Th2免疫应答的良好平衡。值得注意的是，舌下接种J8-VLP会在唾液中引起高水平的IgA抗体。粘膜佐剂霍乱毒素（CT）的共同给药进一步增强了由J8-VLPs制剂诱导的唾液IgA抗体水平的增加。而且，在施用J8-VLP的CT佐剂FD制剂（FD-J8-VLP）和J8-VLP的非FD制剂后观察到的唾液IgA和血清IgG水平是可比的。实际上，从用CT免疫J8-VLP和FD-J8-VLP免疫的小鼠中分离出的唾液在体外显示出对GAS的调理活性。因此，我们观察到，微生物生产的模块化VLP的舌下递送FD制剂可以以经济有效的方式预防和控制流行地区的GAS疾病。 （C）2016 Elsevier Ltd.保留所有权利。

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