DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity
DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity
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DOI：
10.1016/j.vaccine.2007.05.052
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发表时间：
2007-08-10
期刊：
影响因子：
5.5
通讯作者：
Buonaguro, F. M.
中科院分区：
文献类型：
--
作者：
Buonaguro, L.;Devito, C.;Buonaguro, F. M.
已在小鼠模型中通过鼻内（i. n）评价了对呈现乌干达GP 120进化枝A的HIV-1病毒样颗粒（VLP）的免疫反应通过VLP + VLP同源或DNA + VLP异源初免-加强免疫方案（包括HIV-1 DNA gp 160/rev质粒）施用。此外，还评估了基于Eurocine脂质的粘膜L3佐剂对VLP免疫原性的影响，与同源方案相比，所设计的异源方案能够增加env特异性的不道德和细胞免疫应答，这在一定程度上通过施用L3佐剂化的VLP加强剂量而增加。来自免疫动物的免疫血清对异源A和B进化枝病毒分离株表现出> 50%的离体中和活性。包膜B-细胞表位定位显示，在beteroblastin初免-加强免疫策略中，针对整个C2-V5区域的V3表位的应答增强。在粘膜部位诱导体液免疫是极其相关的，粘膜部位代表HIV-1感染的主要入口。在此框架下，DNA-VLP异源初免-加强方案似乎是一种有前景的预防性疫苗方法，其可以显著受益于特定的粘膜佐剂，如Eurocine L3。(c)2007爱思唯尔有限公司保留所有权利。
The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp 120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp 160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well.The designed heterologous protocol is able to increase the env-specific Immoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted.Immune sera from immunized animals exhibit > 50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the beterologous prime-boost immunization strategy.The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. (c) 2007 Elsevier Ltd. All rights reserved.