Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus.
Immune Responses to Orally Administered Recombinant Lactococcus lactis Expressing Multi-Epitope Proteins Targeting M Cells of Foot-and-Mouth Disease Virus.
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口服表达针对口蹄疫病毒 M 细胞的多表位蛋白的重组乳酸乳球菌的免疫反应
DOI：
10.3390/v13102036
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发表时间：
2021-10-09
期刊：
影响因子：
--
通讯作者：
Pan L
中科院分区：
文献类型：
--
作者：
Zhang F;Zhang Z;Li X;Li J;Lv J;Ma Z;Pan L
口蹄疫病毒（FMDV）通过粘膜表面传播，也可通过气溶胶、直接接触和污染物传播。因此，粘膜免疫可以有效地抑制病毒定植。由于疫苗物质进入免疫部位对于有效的口腔黏膜疫苗接种很重要，因此M细胞靶向方法对于有效的疫苗接种很重要，因为M细胞对于腔内抗原流入粘膜淋巴组织至关重要。本研究通过M细胞靶向配体Co1与FMDV的多表位TB1偶联获得TB1-Co1，以提高多表位蛋白抗原TB1的递送效率。乳酸乳球菌（L. lactis）被设计表达异种抗原，作为疫苗载体，具有引发粘膜和全身免疫反应的能力。我们成功构建了能够表达甲型口蹄疫病毒多表位抗原蛋白（TB1和TB1- co1）的重组乳酸菌（L. lactis），命名为乳酸菌-TB1和乳酸菌-TB1- co1。然后，我们研究了构建的重组乳酸乳杆菌在小鼠和豚鼠中的免疫原性。口服乳杆菌tb1和乳杆菌tb1 - co1可有效诱导小鼠粘膜分泌IgA （SIgA）和IgG分泌，产生强烈的细胞免疫反应，脾脏T淋巴细胞大量增殖，上调IL-2、IFN-γ、IL-10和IL-5水平。与单独口服TB1相比，口服配体共轭TB1分别促进了全身和粘膜表面的特异性IgG和SIgA反应。然后，将乳酸菌- tb1 - co1加佐剂CpG-ODN（三种不同剂量）、乳酸菌- tb1 - co1和PBS口服给豚鼠接种。与对照组相比，经乳杆菌lactis-TB1-Co1 +佐剂CpG-ODN和乳杆菌lactis-TB1-Co1免疫的动物血清抗原特异性IgG、IgA、中和抗体和黏膜SIgA水平升高。特别是在小鼠中，乳杆菌tb1 - co1比乳杆菌tb1表现出更好的免疫效果。因此，L. lactis-TB1-Co1可诱导粘膜及全身免疫反应升高，在一定程度上对FMDV具有保护作用。综上所述，M细胞靶向方法可用于开发有效的口蹄疫口腔黏膜疫苗。
Foot and mouth disease virus (FMDV), whose transmission occurs through mucosal surfaces, can also be transmitted through aerosols, direct contact, and pollutants. Therefore, mucosal immunity can efficiently inhibit viral colonization. Since vaccine material delivery into immune sites is important for efficient oral mucosal vaccination, the M cell-targeting approach is important for effective vaccination given M cells are vital for luminal antigen influx into the mucosal lymph tissues. In this study, we coupled M cell-targeting ligand Co1 to multi-epitope TB1 of FMDV to obtain TB1-Co1 in order to improve delivery efficiency of the multi-epitope protein antigen TB1. Lactococcus lactis (L. lactis) was engineered to express heterologous antigens for applications as vaccine vehicles with the ability to elicit mucosal as well as systemic immune responses. We successfully constructed L. lactis (recombinant) with the ability to express multi-epitope antigen proteins (TB1 and TB1-Co1) of the FMDV serotype A (named L. lactis-TB1 and L. lactis-TB1-Co1). Then, we investigated the immunogenic potential of the constructed recombinant L. lactis in mice and guinea pigs. Orally administered L. lactis-TB1 as well as L. lactis-TB1-Co1 in mice effectively induced mucosal secretory IgA (SIgA) and IgG secretion, development of a strong cell-mediated immune reactions, substantial T lymphocyte proliferation in the spleen, and upregulated IL-2, IFN-γ, IL-10, and IL-5 levels. Orally administered ligand-conjugated TB1 promoted specific IgG as well as SIgA responses in systemic and mucosal surfaces, respectively, when compared to orally administered TB1 alone. Then, guinea pigs were orally vaccinated with L. lactis-TB1-Co1 plus adjuvant CpG-ODN at three different doses, L. lactis-TB1-Co1, and PBS. Animals that had been immunized with L. lactis-TB1-Co1 plus adjuvant CpG-ODN and L. lactis-TB1-Co1 developed elevated antigen-specific serum IgG, IgA, neutralizing antibody, and mucosal SIgA levels, when compared to control groups. Particularly, in mice, L. lactis-TB1-Co1 exhibited excellent immune effects than L. lactis-TB1. Therefore, L. lactis-TB1-Co1 can induce elevations in mucosal as well as systemic immune reactions, and to a certain extent, provide protection against FMDV. In conclusion, M cell-targeting approaches can be employed in the development of effective oral mucosa vaccines for FMDV.
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影响因子：
6.4
作者：
Lee HB;Piao DC;Lee JY;Choi JY;Bok JD;Cho CS;Kang SK;Choi YJ
通讯作者：
Choi YJ
影响因子：
4.4
作者：
Kim, Sae-Hae;Seo, Ki-Weon;Jang, Yong-Suk
通讯作者：
Jang, Yong-Suk
影响因子：
9.2
作者：
Amacker, Mario;Smardon, Charli;Fleury, Sylvain
通讯作者：
Fleury, Sylvain
磷酸化川牛膝多糖通过促进树突状细胞成熟发挥佐剂作用
影响因子：
4.6
作者：
Feng，Haibo;McDonough，Sean P.;Chang，Yung-Fu
通讯作者：
Chang，Yung-Fu
影响因子：
5.4
作者：
Blanco, E;Garcia-Briones, M;Sobrino, F
通讯作者：
Sobrino, F