An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci
An inducible surface presentation system improves cellular immunity against human papillomavirus type 16 E7 antigen in mice after nasal administration with recombinant lactococci
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DOI：
10.1099/jmm.0.05472-0
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发表时间：
2004-05-01
影响因子：
3
通讯作者：
Langella, P
中科院分区：
文献类型：
--
作者：
Bermúdez-Humarán, LG;Cortes-Perez, NG;Langella, P
人乳头瘤病毒16型（HPV-16）是宫颈癌的主要病原体。迄今为止，针对HPV-16的疫苗策略是基于E7癌蛋白引发针对该病毒的免疫应答的能力。在这项研究中，使用诱导型或组成型系统，以产生HPV-16 E7蛋白的乳酸乳球菌，一种非致病性和非侵入性革兰氏阳性菌，进行了比较。用诱导系统获得最高的E7产量。当用表达诱导型或组成型E7的重组乳球菌鼻内免疫小鼠时，诱发抗原特异性细胞应答（即IL 2和IFN-γ细胞因子的分泌），并且在接受L.用诱导系统表达E7的乳酸菌。由于细菌抗原的位置可能影响免疫应答，因此重组L.评价了在三个细胞位置（细胞内、分泌或细胞壁锚定）产生E7的乳酸菌菌株。以L.乳酸菌产生可诱导的细胞壁锚定形式的E7蛋白。这些有希望的结果代表了一个新的，安全的粘膜载体的发展，以治疗HPV相关的宫颈癌的一步。
Human papillomavirus type 16 (HPV-16) is the major causative agent of cervical cancer. To date, vaccine strategies against HPV-16 are based on the ability of the E7 oncoprotein to elicit an immune response against this virus. In this study, the use of an inducible or a constitutive system to produce the HPV-16 E7 protein in Lactococcus lactis, a non-pathogenic and non-invasive Gram-positive bacterium, was compared. The highest E7 production was obtained with the inducible system. When mice were immunized intranasally with recombinant lactococci expressing either inducible or constitutive E7, an antigen-specific cellular response (i.e. secretion of IL2 and IFN-gamma cytokines) was evoked and was substantially higher in mice receiving L. lactis expressing E7 with the inducible system. As bacterial antigen location may influence the immune response, recombinant L. lactis strains that produced E7 in three cellular locations, intracellular, secreted or cell-wall-anchored were evaluated. The highest immune response was elicited by administration of L. lactis producing an inducible cell-wall-anchored form of E7 protein. These promising results represent a step towards the development of a new, safe mucosal vector to treat HPV-related cervical cancer.