Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection.
Neonatal mucosal immunization with a non-living, non-genetically modified Lactococcus lactis vaccine carrier induces systemic and local Th1-type immunity and protects against lethal bacterial infection.
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新生儿和婴儿安全有效的免疫接种可以显著降低儿童死亡率，但常规疫苗在刺激新生儿免疫系统方面基本上不成功。我们探索了一种新型粘膜抗原递送系统的能力，该系统由非活体、非遗传修饰的乳酸乳球菌颗粒组成，称为革兰氏阳性增强剂基质（GEM），以诱导新生儿环境中的免疫应答。将鼠疫耶尔森氏菌LcrV作为模型保护性抗原展示在GEM颗粒上。用GEM-LcrV鼻内免疫的新生小鼠产生了LcrV特异性抗体，Th 1型细胞介导的免疫，并保护其免受致死性Y。鼠疫（鼠疫）感染。GEM颗粒在体内和体外均激活并增强新生树突状细胞的成熟。这些树突状细胞表现出增加的促炎和Th 1细胞极化细胞因子分泌、抗原呈递和刺激CD 4+和CD 8 + T细胞的能力。这些数据表明，粘膜免疫L。携带疫苗抗原的乳杆菌GEM颗粒代表了预防生命早期感染性疾病的有希望的方法。
Safe and effective immunization of newborns and infants can significantly reduce childhood mortality, yet conventional vaccines have been largely unsuccessful in stimulating the neonatal immune system. We explored the capacity of a novel mucosal antigen delivery system consisting of non-living, non-genetically modified Lactococcus lactis particles, designated Gram-positive Enhancer Matrix (GEM), to induce immune responses in the neonatal setting. Yersinia pestis LcrV, used as model protective antigen, was displayed on the GEM particles. Newborn mice immunized intranasally with GEM-LcrV developed LcrV-specific antibodies, Th1-type cell-mediated immunity, and were protected against lethal Y. pestis (plague) infection. The GEM particles activated and enhanced the maturation of neonatal dendritic cells both in vivo and in vitro. These dendritic cells showed increased capacities for secretion of pro-inflammatory and Th1-cell polarizing cytokines, antigen presentation and stimulation of CD4+ and CD8+ T cells. These data show that mucosal immunization with L. lactis GEM particles carrying vaccine antigens represents a promising approach to prevent infectious diseases early in life.
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