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Respiratory Immunization With a Whole Cell Inactivated Vaccine Induces Functional Mucosal Immunoglobulins Against Tuberculosis in Mice and Non-human Primates

全细胞灭活疫苗呼吸预防接种诱导小鼠和非人灵长类动物抗结核的功能性粘膜免疫球蛋白

  • 影响因子:4.30
  • DOI:10.3389/fmicb.2020.01339
  • 作者列表:"Nacho Aguilo","Nacho Aguilo","Santiago Uranga","Santiago Uranga","Elena Mata","Elena Mata","Raquel Tarancon","Raquel Tarancon","Ana Belén Gómez","Ana Belén Gómez","Dessislava Marinova","Dessislava Marinova","Isabel Otal","Isabel Otal","Marta Monzón","Juan Badiola","Dolores Montenegro","Eugenia Puentes","Esteban Rodríguez","Richard A. W. Vervenne","Claudia C. Sombroek","Frank A. W. Verreck","Carlos Martín","Carlos Martín","Carlos Martín
  • 发表时间:2020-06-18
Abstract

Vaccination through the natural route of infection represents an attractive immunization strategy in vaccinology. In the case of tuberculosis, vaccine delivery by the respiratory route has regained interest in recent years, showing efficacy in different animal models. In this context, respiratory vaccination triggers lung immunological mechanisms which are omitted when vaccines are administered by parenteral route. However, contribution of mucosal antibodies to vaccine- induced protection has been poorly studied. In the present study, we evaluated in mice and non-human primates (NHP) a novel whole cell inactivated vaccine (MTBVAC HK), by mucosal administration. MTBVAC HK given by intranasal route to BCG-primed mice substantially improved the protective efficacy conferred by subcutaneous BCG only. Interestingly, this improved protection was absent in mice lacking polymeric Ig receptor (pIgR), suggesting a crucial role of mucosal secretory immunoglobulins in protective immunity. Our study in NHP confirmed the ability of MTBVAC HK to trigger mucosal immunoglobulins. Importantly, in vitro assays demonstrated the functionality of these immunoglobulins to induce M. tuberculosis opsonization in the presence of human macrophages. Altogether, our results suggest that mucosal immunoglobulins can be induced by vaccination to improve protection against tuberculosis and therefore, they represent a promising target for next generation tuberculosis vaccines.

摘要

通过自然感染途径接种疫苗代表了疫苗学中一种有吸引力的预防接种。在结核病的情况下,近年来通过呼吸途径递送疫苗重新获得了兴趣,在不同的动物模型中显示出疗效。在这种情况下,呼吸道疫苗接种触发肺免疫机制,当疫苗通过胃肠外途径给药时,这些机制被省略。然而,粘膜抗体对疫苗诱导的保护作用的贡献研究甚少。在本研究中,我们通过粘膜给药在小鼠和非人灵长类动物 (NHP) 中评价了一种新型全细胞灭活疫苗 (MTBVAC HK)。通过鼻内途径给予 BCG 致敏小鼠 MTBVAC HK 可显著提高仅皮下 BCG 赋予的保护效力。有趣的是,这种改善的保护作用在缺乏聚合 Ig 受体 (pIgR) 的小鼠中缺失,提示粘膜分泌免疫球蛋白在保护性免疫中的关键作用。我们在 NHP 中的研究证实了 MTBVAC HK 触发粘膜免疫球蛋白的能力。重要的是,体外试验证明了这些免疫球蛋白在人巨噬细胞存在的情况下诱导结核分枝杆菌调理的功能。总之,我们的结果表明,粘膜免疫球蛋白可以通过疫苗接种来诱导,以提高对结核病的保护作用,因此,它们代表了下一代结核病疫苗的一个有希望的靶点。

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影响因子:6.74700
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