高迁移率族蛋白B1对人乳头瘤病毒重组腺病毒载体疫苗免疫效果的影响

Effect of high mobility group box protein 1 on immune efficacy of recombinant adenovirus vector-based human papiliomavirus-16 vaccine

目的评价高迁移率族蛋白B1（HMGBl）分子对接种HPVl6型重组腺病毒载体疫苗实验小鼠免疫应答和抗肿瘤生物学效应的影响。方法通过TC-1细胞移植诱导建立小鼠肿瘤模型，在接种HPVl6型重组腺病毒载体疫苗的同时，给予外源性HMGBl及其特异性拮抗剂HMGBlAbox注射，进行肿瘤抑制试验、肿瘤细胞挑战实验、特异性IFN1的诱导检测。结果肿瘤抑制试验表明，与单独接种不同剂量疫苗组相比，注射HMGBl后小鼠成瘤率显著提高（2／10VS9／10，P〈0．05）；而注射了A—box则减低了小鼠成瘤率（7／10VS1／10，P〈O．05）。TC-1肿瘤细胞挑战试验显示，10只先接种疫苗的小鼠中有8只免受TC-1肿瘤细胞的攻击，而HMGB1仅能保护2只，且小鼠成瘤时间提前，肿瘤更大，同时HMGB1还使疫苗诱导特异性IFNγ的能力显著降低。结论HMGBl分子可以削弱HPV16型重组腺病毒载体疫苗在小鼠模型上的免疫效果，而其拮抗剂Abox蛋白具有一定程度增强作用。

Objective To evaluate the influence of high mobility group box protein 1 （HMGB1） on immune response and anti-tumor effect of recombinant adenovirus vector-based human papillomavirus （HPV）-16 vaccine in the laboratory mice. Methods The mouse tumor models were established by TC-1 cell transplantation, and were injected exogenous HMGB1 and its antagonist HMGB1 A box. Anti-tumor test, TC-1 tumor cell challenge test and specific IFNγ induction test were carried out with recombinant adenovirus vector-based HPV-16 vaccination. Results The anti-tumor test showed that HMGB1 could promote tumor occurrence （2/10 vs 9/10, P〈O.05）, while A box reduced it （7/10 vs 1/10, P〈0.05）eompared with groups separately inoculating various levels of vaccines. TC-1 tumor cell challenge test showed that 8 mice escaped TC-1 cell attack among 10 mice that had immune response after the vaccination, but HMGB1 intervention only lead to 2 mice escaping TC-1 cell attack ,which had an earlier time of tumor growth and bigger tumor. Meanwhile, the specific IFNT induction by vaccination was weakened by HMGB1. Conclusions HMGB1 can block the immune response and anti-tumor effect of recombinant adenovirus vector-based HPV-16 vaccine in mouse model, while its antagonist A box protein can enhance it partly.