Epithelial stem cells as mucosal antigen-delivering cells: A novel AIDS vaccine approach.
Epithelial stem cells as mucosal antigen-delivering cells: A novel AIDS vaccine approach.
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上皮干细胞作为粘膜抗原递送细胞:一种新的艾滋病疫苗方法。
DOI:
10.1016/j.vaccine.2013.09.006
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发表时间:
2015
期刊:
影响因子:
5.5
通讯作者:
Gauduin,Marie-Claire
中科院分区:
文献类型:
--
作者:
White,Robert;Chenciner,Nicole;Bonello,Gregory;Salas,Mary;Blancou,Philippe;Gauduin,Marie-Claire
A key obstacle limiting development of an effective AIDS vaccine is the inability to deliver antigen for a sufficient period of time resulting in weak and transient protection. HIV transmission occurs predominantly across mucosal surfaces; therefore, an ideal vaccine strategy would be to target HIV at mucosal entry sites to prevent infection. Such a novel strategy relies on the activation of mucosal immune responseviapresentation of viral antigens by the mucosal epithelial cells. The use of a terminally differentiated epithelial cell promoter to drive expression of antigens leading to viral protein production in the upper layers of the epithelium is central to the success of this approach. Our results show that when administered intradermally to mice, a GFP-reporter gene under the transcriptional control of the involucrin promoter is expressed in the upper layers of the epidermis and, although transduced cells were very low in number, high and sustained anti-GFP antibody production is observedin vivo. A subsequent experiment investigates the effectiveness of GFP-tagged replication-competent SIVdeltaNef and GFP-tagged replication-deficient SIVdeltaVifdeltaNef constructs under the transcriptional control of the involucrin promoter. Optimal conditions for production of pseudotyped VSV-G viral particles destined to transduce basal epithelial stem cells at the mucosal sites of entry of SIV in our animal model were determined. Altogether, the data demonstrate the feasibility of an epithelium-based vaccine containing involucrin-driven viral antigen encoding sequences that integrate into epithelial stem cells and show long-term expression in the upper layer of the epithelium even after multiple cycle of epithelia renewal. Such epithelium-based vaccine should elicit a long-term immunity against HIV/SIV infection at the site of entry of the virus.
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DOI:
10.1074/jbc.271.1.512
发表时间:
1996
期刊:
The Journal of Biological Chemistry
影响因子:
--
作者:
E. López;Alfonso Vega;A. Cadena;Sonia E. Granados;L. F. Jave;P. Gariglio;L. M. Alvarez
通讯作者:
L. M. Alvarez
影响因子:
5.6
作者:
Sommer, P;Vartanian, JP;Wain-Hobson, S
通讯作者:
Wain-Hobson, S
DOI:
10.1073/pnas.95.8.4356
发表时间:
1998-04-14
影响因子:
11.1
作者:
Kolodka, TM;Garlick, JA;Taichman, LB
通讯作者:
Taichman, LB
影响因子:
5.3
作者:
H. Green;F. Watt
通讯作者:
F. Watt
影响因子:
5.5
作者:
Amara, RR;Villinger, F;Robinson, HL
通讯作者:
Robinson, HL