%0 Journal Article
%T Anti-gp120 Minibody Gene Transfer to Female Genital Epithelial Cells Protects against HIV-1 Virus Challenge In Vitro
%A Ussama M. Abdel-Motal
%A Phuong T. N. Sarkis
%A Thomas Han
%A Jeffery Pudney
%A Deborah J. Anderson
%A Quan Zhu
%A Wayne A. Marasco
%J PLOS ONE
%D 2011
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0026473
%X Background 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. Methods and Findings 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 ˇ°minibodyˇ± 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. Conclusion 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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026473