Journal
VACCINE
Volume 36, Issue 24, Pages 3423-3426Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2018.05.009
Keywords
Human papillomavirus (HPV); Therapeutic HPV vaccine; Mucosal immunity; Cervical intraepithelial neoplasia (CIN); Cervical cancer; Lactobacillus-based vaccine
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Funding
- Japan Agency for Medical Research and Development (AMED), Japan [151k0201019h0003]
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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.
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