Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.
Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro.
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DOI：
10.1371/journal.pone.0026473
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Marasco WA
中科院分区：
文献类型：
--
作者：
Abdel-Motal UM;Sarkis PT;Han T;Pudney J;Anderson DJ;Zhu Q;Marasco WA
Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb) that block HIV-1 entry would provide an important new intervention that could slow the spread of HIV/AIDS. This study tested the hypothesis that adeno-associated virus (AAV)-BnAb gene transfer to cervico-vaginal epithelial cells will lead to protection against HIV-1. Accordingly, a recombinant AAV vector that encodes human b12 anti-HIV gp120 BnAb as a single-chain variable fragment Fc fusion (scFvFc), or “minibody” was constructed. The secreted b12 minibody was shown to be biologically functional in binding to virus envelope protein, neutralizing HIV-1 and importantly, blocking transfer and infectivity of HIV-1bal in an organotypic human vaginal epithelial cell (VEC) model. Furthermore, cervico-vaginal epithelial stem cells were found to be efficiently transduced by the optimal AAV serotype mediated expression of GFP. This study provides the foundation for a novel microbicide strategy to protect against sexual transmission of HIV-1 by AAV transfer of broadly neutralizing antibody genes to cervico-vaginal epithelial stem cells that could replenish b12 BnAb secreting cells through multiple menstrual cycles.
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影响因子：
--
作者：
Novak, Richard M.;Donoval, Betty A.;Landay, Alan
通讯作者：
Landay, Alan
影响因子：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
DOI：
10.1111/j.1600-0897.2007.00561.x
发表时间：
2008-01-01
影响因子：
3.6
作者：
Cole, Alexander M.;Cole, Amy Liese
通讯作者：
Cole, Amy Liese
影响因子：
32.4
作者：
Bobardt, MD;Saphire, ACS;Gallay, PA
通讯作者：
Gallay, PA
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF