TITLE

Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer

AUTHOR(S)
Abdel-Motal, U M; Harbison, C; Han, T; Pudney, J; Anderson, D J; Zhu, Q; Westmoreland, S; Marasco, W A
PUB. DATE
September 2014
SOURCE
Gene Therapy;Sep2014, Vol. 21 Issue 9, p802
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques (Rh) can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. Gene transfer studies demonstrated that, of various green fluorescent protein (GFP)-expressing AAV serotypes, AAV-6 most efficiently transduced freshly immortalized and primary genital epithelial cells (PGECs) of female Rh in vitro. In addition, AAV-6-b12 minibody transduction of Rh PGECs led to inhibition of SHIV162p4 transmigration and virus infectivity in vitro. AAV-6-GFP could also successfully transduce vaginal epithelial cells of Rh when applied intravaginally, including p63+ epithelial stem cells. Moreover, intravaginal application of AAV-6-b12 to female Rh resulted in prolonged minibody detection in their vaginal secretions throughout the 79-day study period. These data provide proof of principle that AAV-6-mediated delivery of anti-HIV broadly neutralizing antibody (BnAb) genes to the lower genital tract of female Rh results in persistent minibody detection for several months. This strategy offers promise that an anti-HIV-1 genetic microbicide strategy may be possible in which topical application of AAV vector, with periodic reapplication as needed, may provide sustained local BnAb expression and protection.
ACCESSION #
97870542

 

Related Articles

  • Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Caines, Matthew E C; Bichel, Katsiaryna; Price, Amanda J; McEwan, William A; Towers, Greg J; Willett, Brian J; Freund, Stefan M V; James, Leo C // Nature Structural & Molecular Biology;Apr2012, Vol. 19 Issue 4, p411 

    Rhesus macaque TRIMCyp (RhTC) is a potent primate antiviral host protein that inhibits the replication of diverse HIV viruses. Here we show that it has acquired the ability to target multiple viruses by evolving an active site that interconverts between multiple conformations. Mutations that...

  • Conformational Adaptation of Asian Macaque TRIMCyp Directs Lineage Specific Antiviral Activity.  // PLoS Pathogens;Aug2010, Vol. 6 Issue 8, p1 

    No abstract available.

  • Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques. Titanji, Kehmia; Velu, Vijayakumar; Chennareddi, Lakshmi; Vijay-Kumar, Matam; Gewirtz, Andrew T.; Freeman, Gordon J.; Amara, Rama R. // Journal of Clinical Investigation;Nov2010, Vol. 120 Issue 11, p3878 

    Rapid progression to AIDS is a significant problem, especially in developing countries, where the majority of HIV-infected individuals reside. As rapid disease progression is also frequently observed in SIV-infected macaques, they represent a valuable tool to investigate the pathogenesis of this...

  • Gene transfer to the rhesus monkey brain using SV40-derived vectors is durable and safe. Louboutin, J-P; Marusich, E; Fisher-Perkins, J; Dufour, J P; Bunnell, B A; Strayer, D S // Gene Therapy;Jul2011, Vol. 18 Issue 7, p682 

    Gene transfer to central nervous system (CNS) has been approached using various vectors. Recombinant SV40-derived vectors (rSV40s) transduce human neurons and microglia effectively in vitro and in rodent brains in vivo, so we tested rSV40s gene transfer to rhesus monkey CNS in vivo, to...

  • Silencing of HIV-1 genes using siRNA-expressing genetic constructs. Tchurikov, N. A.; Gashnikova, N. M.; Kretova, O. V.; Pokrovsky, A. G. // Molecular Biology;Sep2006, Vol. 40 Issue 5, p702 

    The article presents a research report on the silencing of HIV-1 genes using siRNA-expressing genetic constructs. The RNA interference is known to be a powerful natural mechanism involved in gene expression and protection of cells against foreign RNA. The procedure followed and the results...

  • Ultra Structural Characterisation of Tetherin - a Protein Capable of Preventing Viral Release from the Plasma Membrane. Gupta, Ravindra K.; Towers, Greg J. // Viruses (1999-4915);Apr2010, Vol. 2 Issue 4, p987 

    Tetherin is an antiviral restriction factor made by mammalian cells to protect them from viral infection. It prevents newly formed virus particles from leaving infected cells. Its antiviral mechanism appears to be remarkably uncomplicated. In 2 studies published in PLoS Pathogens electron...

  • Impaired type I and type III interferon induction and rhinovirus control in human cystic fibrosis airway epithelial cells. Vareille, Marjolaine; Kieninger, Elisabeth; Alves, Marco P.; Kopf, Brigitte S.; Moller, Alexander; Geiser, Thomas; Johnston, Sebastian L.; Edwards, Michael R.; Regamey, Nicolas // Thorax;Jun2012, Vol. 67 Issue 6, p517 

    BackgroundRhinoviruses are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to rhinovirus-induced CF exacerbations are poorly understood. It is hypothesised that there is a deficient innate...

  • Potent Immune Responses in Rhesus Macaques Induced by Nonviral Delivery of a Self-amplifying RNA Vaccine Expressing HIV Type 1 Envelope With a Cationic Nanoemulsion. Bogers, Willy M.; Oostermeijer, Herman; Mooij, Petra; Koopman, Gerrit; Verschoor, Ernst J.; Davis, David; Ulmer, Jeffrey B.; Brito, Luis A.; Cu, Yen; Banerjee, Kaustuv; Otten, Gillis R.; Burke, Brian; Dey, Antu; Heeney, Jonathan L.; Shen, Xiaoying; Tomaras, Georgia D.; Labranche, Celia; Montefiori, David C.; Liao, Hua-Xin; Haynes, Barton // Journal of Infectious Diseases;Mar2015, Vol. 211 Issue 6, p947 

    Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well suited for global health applications. The SAM vaccine platform is based on a synthetic,...

  • Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication. Barsov, Eugene V.; Trivett, Matthew T.; Minang, Jacob T.; Sun, Haosi; Ohlen, Claes; Ott, David E. // PLoS ONE;2011, Vol. 6 Issue 8, p1 

    Background: The SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8+ T-cell control of SIV replication in CD4+ T cells, we asked whether TCRs isolated from rhesus macaque CD8+...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics