Abstract

Evaluation of Pre-Clinical Efficacy to HPV16 L2E6E7 Vaccine and HPV16 E6E7 Adenovirus-5 Vector Vaccine with Different Dosages and Prime- Booster Regiments in Mouse Model

Zhuang Fang-Cheng, Chen Gang, Wu Jie, Jin Su-feng, Jiang Yun-shui, Gao Men, Li Jian-buo, Zhao Li, Mao Zian and Tian Houwen

Purpose: This study evaluates the dose-response and immunization procedure in mouse model and the efficacy of prime-booster regimens with HPV16 L2E6E7 vaccine and HPV16 E6E7 Ad5 vector vaccine. Methods: Experimental animals were C57 BL/6 mice. Each group included 10 or 20 C57 BL/6 mice. The tumor model used TC-1 tumor cells. The HPV16 L2E6E7 vaccine groups were treated using the following dosage: 15 μg/ml, 30 μg/ml, 60 μg/ml, 120 μg/ml, 240 μg/ml, and then 120 μg/ml was used for the following regimens: 0-7 days, 0-15 days, 0-7-15 days. The HPV16 E6E7 Adenovirus-5 vector vaccine groups were treated using the following dosage: 3.00×106 IU/ml, 3.00×107 IU/ml, 3.00×108 IU/ml, 3.00×109 IU/ml, and then 3.00×107 IU/ml was used for the following regimens: 0-7 days, 0-15 days, 0-7-15 days, and control group. Prime-booster combined regimens with HPV L2E6E7 vaccine (P, 120 μg/ml) and HPV16 E6E7 ad5 vector vaccine (V, 3.00×107 IU/ml) were set as follows: 0P-7P days, 0P-7V days, and 0P-7P-15V days, 0P-7V-15V days, and 0P-7P-15V-21V days. Results: Upon challenge with 104 TC-1 tumor cells, mice developed palpable, rapidly growing tumors within 7–14 days. These tumors became lethal to the mice within 21–28 days. HPV16 L2E6E7 vaccine (120 μg/ml, 0-7- 15 day’s procedure) protective efficacy was 85% and the HPV16 E6E7 Ad5 vector vaccine (3.00×107 IU/ml, 0 day procedure) that was 80%. Prime-booster regimens showed a protective efficacy of 80–90% for the 0P-7V days and 0P-7V-15V day’s schedules. Conclusion: HPV16 L2E6E7 vaccine and HPV16 E6E7 Ad5 vector vaccine are proved the candidate vaccine for therapeutic intervention against HPV16-induced tumor.