Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells

被引：46

作者：

Komatsu, Atsushi ^{[1
,2
]}

Igimi, Shizunobu ^{[3
]}

Kawana, Kei ^{[1
,2
]}

机构：

[1] Nihon Univ, Sch Med, Dept Obstet & Gynecol, Itabashi Ku, 30-1 Oyaguchi Kamimachi, Tokyo 1738610, Japan

[2] Univ Tokyo, Fac Med, Dept Obstet & Gynecol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan

[3] Tokyo Univ Agr, Dept Appl Biol & Chem, Setagaya Ku, I-1-1 Sakuragaoka, Tokyo 1568502, Japan

来源：

VACCINE | 2018年 / 36卷 / 24期

关键词：

Human papillomavirus (HPV); Therapeutic HPV vaccine; Mucosal immunity; Cervical intraepithelial neoplasia (CIN); Cervical cancer; Lactobacillus-based vaccine; CERVICAL INTRAEPITHELIAL NEOPLASIA; HIGH-GRADE; PHASE-II; TRIAL; LESIONS; E7; STRATEGY; CASEI; WOMEN;

D O I：

10.1016/j.vaccine.2018.05.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Therapeutic HPV vaccine is an agent to induce E7-specific Th1 immune responses to treat cervical neoplasia (CIN2-3). Our previous clinical trial has demonstrated that oral administration of HPV16 E7-expressing Lactobacillus casei (L. casei), GLBL101c, resulted in the regression of HPV16-related CIN3. Here we examined optimization of the E7-expressing L. casei for induction of the mucosal immune responses to E7. Various doses of HPV16 E7 molecule were displayed on the L casei. Immunization with E7-bound L. casei showed the induction of E7-specific mucosal IFNy-producing cells was dependent on displayed E7-doses but saturated beyond 0.3 mu/10(8) cells. A new agent, L casei with endogenous expression of E7 (IGMKK16E7), showed the optimal amount of displayed-E7. Immunization with IGMKK16E7 demonstrated 4-fold higher induction of E7-specific mucosal IFNy-producing cells when compared with the former one. Our new system provided the optimal E7-expressing L casei for displayed-E7 amount and induction of mucosal Th1 immune response. (C) 2018 Elsevier Ltd. All rights reserved.

引用

页码：3423 / 3426

页数：4

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