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Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro

Abdel-Motal, Ussama M ; Sarkis, Phuong T N ; Han, Thomas ; Pudney, Jeffery ; Anderson, Deborah J ; Zhu, Quan ; Marasco, Wayne A Zhang, Luwen

PloS one, 2011-10, Vol.6 (10), p.e26473-e26473 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro
Autor: Abdel-Motal, Ussama M ; Sarkis, Phuong T N ; Han, Thomas ; Pudney, Jeffery ; Anderson, Deborah J ; Zhu, Quan ; Marasco, Wayne A
Zhang, Luwen
Assuntos: Acquired immune deficiency syndrome ; AIDS ; Analysis ; Antibodies ; Antiviral agents ; Binding sites ; Biology ; Blocking ; Cancer ; Cell Line ; Cell surface ; Disease transmission ; Epithelial cells ; Epithelial Cells - metabolism ; Epithelial Cells - virology ; Female ; Gene therapy ; Gene transfer ; Genes ; Genital tract ; Genitalia, Female - cytology ; Glycoprotein gp120 ; Glycoproteins ; Gynecology ; Health aspects ; Heparan sulfate ; HIV ; HIV (Viruses) ; HIV Antibodies - genetics ; HIV Antibodies - metabolism ; HIV Envelope Protein gp120 - immunology ; HIV Infections - immunology ; HIV Infections - prevention & control ; HIV-1 - immunology ; HIV-1 - metabolism ; Human immunodeficiency virus ; Humans ; Humoral immunity ; Immunity ; Immunology ; Infection ; Infections ; Infectivity ; Medical schools ; Medicine ; Menstruation ; Mucosa ; Mucosal immunity ; Neutralizing ; Obstetrics ; Penicillin ; Protein binding ; Rodents ; Sexual transmission ; Sexually transmitted diseases ; STD ; Stem cells ; Vagina ; Viral antibodies ; Viral envelope proteins ; Viral infections ; Viruses
É parte de: PloS one, 2011-10, Vol.6 (10), p.e26473-e26473
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Conceived and designed the experiments: UMA PS TH. Performed the experiments: UMA PS TH JP. Analyzed the data: UMA PS QZ. Contributed reagents/materials/analysis tools: TH DA. Wrote the paper: UMA PS WM.
Descrição: 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-1(bal) 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.
Editor: United States: Public Library of Science
Idioma: Inglês

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Anti-gp120 minibody gene transfer to female genital epithelial cells protects against HIV-1 virus challenge in vitro

Abdel-Motal, Ussama M ; Sarkis, Phuong T N ; Han, Thomas ; Pudney, Jeffery ; Anderson, Deborah J ; Zhu, Quan ; Marasco, Wayne A Zhang, Luwen

United States: Public Library of Science

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