The adjuvant effect of bacterium-like particles depends on the route of administration.
The adjuvant effect of bacterium-like particles depends on the route of administration.
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DOI：
10.3389/fimmu.2023.1082273
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发表时间：
2023
影响因子：
7.3
通讯作者：
Inoue, Naoki
中科院分区：
文献类型：
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作者：
Sudo, Haruka;Tokunoh, Nagisa;Tsujii, Ayato;Kawashima, Sarana;Hayakawa, Yuta;Fukushima, Hiroki;Takahashi, Keita;Koshizuka, Tetsuo;Inoue, Naoki
关键词：
将疫苗直接施用至粘膜表面，例如通过口服或鼻接种，代表了对当前肠胃外接种的有吸引力的替代或补充，因为其具有在粘膜和全身组织诱导抗原特异性免疫的潜力。虽然细菌样颗粒（BLP），来自乳酸菌的肽聚糖结构，已被研究作为一种新的佐剂口服或鼻腔疫苗，它仍然不清楚是否不同的管理途径的BLP的佐剂效果。在这里，我们表明，从乳酸乳球菌NZ 9000的BLP的佐剂效果是更大的鼻腔给药比口服给药。我们将BLP与啮齿类柠檬酸杆菌的毒力因子Tir结合，作为模型免疫-抗原复合物，发现用BLP-Tir鼻内而非口服免疫小鼠可在呼吸道和肠粘膜诱导强大的抗原特异性伊加应答、IgG 2b偏斜的全身应答和Th 17细胞应答。作为潜在的机制之一，我们证明了经鼻给药比经口给药具有更高的BLP结合抗原向粘膜相关淋巴组织的递送效率（约1，000倍）。此外，BLP-Tir的鼻给药而非口服给药引起了强有力的先天免疫应答，其特征在于粘膜相关淋巴组织中各种促炎细胞因子和趋化因子的表达。综合考虑这些发现，我们预计BLP可以成为鼻疫苗的一种有吸引力的新型佐剂，不仅针对呼吸道传染病，还针对胃肠道传染病。
Direct administration of vaccines to mucosal surfaces, such as via oral or nasal vaccination, represents an attractive alternative, or complement, to current parenteral vaccination because it has a potential to induce antigen-specific immunity both at mucosal and systemic tissues. Although bacterium-like particles (BLPs), peptidoglycan structures derived from lactic acid bacteria, have been investigated as a novel adjuvant for oral or nasal vaccines, it remains unclear whether the administration routes differ the adjuvant effect of BLPs. Here, we showed that the adjuvant effect of BLPs from Lactococcus lactis NZ9000 is greater with the nasal administration than with the oral administration. We conjugated BLPs with Tir, a virulence factor of Citrobacter rodentium, as a model adjuvant-antigen complex, and found that nasal, but not oral, immunization of mice with BLP-Tir induced robust antigen-specific IgA responses at the respiratory and intestinal mucosa, IgG2b-skewed systemic responses, and Th17 cellular responses. As one of the underlying mechanisms, we demonstrated that the nasal administration has a greater delivery efficiency (~1,000-fold) of the BLPs-conjugated antigens to mucosal-associated lymphoid tissues than the oral administration. Furthermore, the nasal, but not oral, administration of BLP-Tir elicited robust innate immune responses that were characterized by the expression of various pro-inflammatory cytokines and chemokines in the mucosal-associated lymphoid tissues. Considering these findings together, we anticipate that BLPs can be an attractive novel adjuvant for nasal vaccines targeting not only respiratory but also gastrointestinal infectious diseases.
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影响因子：
5.5
作者：
Keijzer, C.;Haijema, B. J.;Broere, F.
通讯作者：
Broere, F.
影响因子：
6.7
作者：
Dileepan T;Linehan JL;Moon JJ;Pepper M;Jenkins MK;Cleary PP
通讯作者：
Cleary PP
影响因子：
4
作者：
Heine SJ;Franco-Mahecha OL;Chen X;Choudhari S;Blackwelder WC;van Roosmalen ML;Leenhouts K;Picking WL;Pasetti MF
通讯作者：
Pasetti MF
影响因子：
5.4
作者：
Deenick, EK;Hasbold, J;Hodgkin, PD
通讯作者：
Hodgkin, PD
影响因子：
8
作者：
通讯作者：
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