Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Abdel-Motal UM

PROVIDER: S-EPMC3198777 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Abdel-Motal Ussama M UM Sarkis Phuong T N PT Han Thomas T Pudney Jeffery J Anderson Deborah J DJ Zhu Quan Q Marasco Wayne A WA

PloS one 20111021 10

<h4>Background</h4>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.<h4>Methods and findings</h4>This study tested the hyp ...[more]

PMID: 22031835

Similar Datasets

Project description:Chlamydia spp. productively infect mucosal epithelial cells of multiple anatomical sites, including the conjunctiva, lungs, gastrointestinal (GI) tract, and urogenital tract. We, and others, previously established that chlamydial GI tropism is mediated by distinct chromosomal and plasmid factors. In this study, we describe a genital infection-attenuated Chlamydia muridarum mutant (GIAM-1) that is profoundly and specifically attenuated in the murine genital tract. GIAM-1 infected the murine GI tract similarly to wild-type (WT) Chlamydia muridarum but did not productively infect the lower genital tract of female mice, ascend to infect the upper genital tract, or cause hydrosalpinx. However, GI infection of mice with GIAM-1 elicited a transmucosal immune response that protected against subsequent genital challenge with WT Chlamydia muridarum Collectively, our results demonstrate that chlamydia mutants that are profoundly attenuated for specific organ tissues can be derived and demonstrate that live-attenuated vaccine strains that infect the GI tract, but do not elicit genital tract disease, could be used to protect against chlamydia genital tract infection and disease.IMPORTANCE Chlamydia is the most common sexually transmitted bacterial infection in the United States. Most chlamydia genital infections resolve without serious consequences; however, untreated infection in women can cause pelvic inflammatory disease and infertility. Antibiotics are very effective in treating chlamydia, but most genital infections in both men and women are asymptomatic and go undiagnosed. Therefore, there is a critical need for an effective vaccine. In this work, we show that a mutant chlamydia strain, having substantially reduced virulence for genital infection, colonizes the gastrointestinal tract and produces robust immunity to genital challenge with fully virulent wild-type chlamydia. These results are an important advance in understanding chlamydial virulence and provide compelling evidence that safe and effective live-attenuated chlamydia vaccines may be feasible.

Project description:BackgroundThe practice of Female Genital Mutilation (FGM) is a deeply-rooted tradition in 30 Sub-Saharan and Middle-East countries which affects approximately 200 million women and girls worldwide. The practice leads to devastating consequences on the health and quality of life of women and girls in both the short and long term. Globalizing processes and migration flows have recorded cases of this practice worldwide representing for healthcare professionals an emerging challenge on how to approach their healthcare in a transcultural, ethical and respectful way. No survey to assess knowledge, attitudes and practices on FGM among primary healthcare professionals has been conducted in the Valencian region of Spain to date.MethodsThe main purpose of this study is to assess the perceptions, knowledge, practices and attitudes of the primary healthcare professionals in relation to FGM in the Clínic-Malvarrosa healthcare area of Valencia. A cross-sectional descriptive study was conducted based on a self-administered questionnaire to general practitioners, paediatricians, nurses, midwives, gynaecologists, social workers and others.ResultsA total of 321 professionals answered the questionnaire. Less than 5% of professionals answered that they had ever found a case of FGM during their professional practice and 21.8% answered that they had ever worked with population at risk of FGM. Almost 15% of professionals answered that they had received training on FGM but of those who had received training, only 22.7% correctly identified the typology of FGM and less than 5% correctly identified the geographical area. Only 6.9% of the respondents admitted to know some protocol of action, being midwives, paediatricians and social workers the most aware professionals of such protocols.ConclusionThis study demonstrates that FGM is a problem present in the population attending primary healthcare services in Valencia. However, the professionals showed a profound lack of knowledge around concept, typology, countries of prevalence of FGM and existent protocols of action. It is healthcare professional duty to recognize this situation and to follow the right protocols of action, refer these women and their families to the most appropriate services and professionals that fit their needs, ensuring a multidisciplinary, positive and transcultural care for these families.

Project description:BackgroundUnderstanding women's perspectives of female genital cutting is particularly critical for understanding the roots of the problem and enhancing effectiveness of any prevention program. Very limited research has examined how people in Iraqi Kurdistan Region think about this practice. This study aimed to explore the perspectives of women of female genital cutting with the aim of uncovering discrepancies and commonalities between women of different socio-educational groups.MethodsAn explorative study using Q-methodology was conducted with 29 women from different educational and socio-economic statuses in Erbil, the main city of the Iraqi Kurdistan Region. Participants were asked to rank-order a set of 39 statements about different aspects of female genital cutting into a distribution on a scale of nine from "disagree most" to "agree most". By-person factor analysis was performed with factors or latent viewpoints extracted through centroid method and varimax rotation.ResultsA four-factor solution and one consensus perspective provided the best conceptual fit for the women's perspectives about female genital cutting. Factor 1, entitled "positive cultural tradition", centers on recognizing female genital cutting as a positive cultural aspect and an essential part of the Kurdish culture. Factor 2, "active opponents", positions around actively opposing the practice of female genital cutting and considering the practice a violation of human rights. Factor 3, "role of law", stresses the importance of developing and enforcing law for combating female genital cutting. Factor 4, "health concerns and passive opposition", represents the perspectives of recognizing the importance of health concerns resulting from female genital cutting and opposition of the practice but not in an active manner. A consensus perspective, "marital role", centers primarily on lack of effect of female genital cutting on women's marital role.ConclusionsFemale genital cutting is still a contentious issue among women in Iraqi Kurdistan Region. By identifying disagreement and consensus among women, four different perspectives on female genital cutting were uncovered with having perspectives at both extremes of accepting the practice and actively opposing it. The study highlighted the typical characterizations that are associated with each perspective.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets