Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers

Doncel, Gustavo F.; Clark, Meredith R.

doi:10.1016/j.antiviral.2010.09.018

Cited by 43 publications

(34 citation statements)

References 79 publications

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“…Over the past decade, a great deal of effort has been devoted to developing anti-HIV microbicides that can effectively prevent virus transmission (35,76,85,102,154). With the exception of the CAPRISA 004 trial (2), most microbicide trials conducted to date have failed due to a number of factors, including poor adherence (141) and unexpected inflammation that increased the risk of transmission (1,(39)(40)(41)(148)(149)(150).…”

Section: Nr Ligands Inhibit Hiv-1 Replication In Primary Macrophagesmentioning

confidence: 99%

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Hanley

Viglianti

2011

J Virol

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Section: Nr Ligands Inhibit Hiv-1 Replication In Primary Macrophagesmentioning

confidence: 99%

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Hanley

Viglianti

2011

J Virol

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“…29,68,69 Therefore, to prevent these problems the ideal HIV microbicide should combine different classes of antiretroviral drugs acting in different targets with compounds that act in a non-specific way. 18 Here, we have shown that dendrimer/TFV/RAL combinations at a fixed 1:1:1 ratio have significant synergistic interactions against the primary R5-and X4-HIV-2 isolates.…”

Section: Discussionmentioning

confidence: 99%

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

et al. 2015

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“…Women account for over half of all adults living with HIV worldwide, and given the increasing prevalence of new infections in women, the development of prevention alternatives which can be controlled by females is imperative. A number of agents have been proposed and/or tested as a topical therapy to prevent HIV infection, including nonspecific inhibitors and specific anti-HIV inhibitors (1,8,9,18,31,32). Though there has been modest success, additional inhibitors and delivery systems are required for sustained prevention of infection.…”

mentioning

confidence: 99%

Enhanced Neutralization of HIV by Antibodies Displayed on the S-Layer of Caulobacter crescentus

Duval

Lewis

Nomellini

et al. 2011

Antimicrob Agents Chemother

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Innovative methods of prevention are needed to stop the more than two million new HIV-1 infections annually, particularly in women. Local application of anti-HIV antibodies has been shown to be effective at preventing infection in nonhuman primates; however, the concentrations needed are cost prohibitive. Display of antibodies on a particulate platform will likely prolong effectiveness of these anti-HIV agents and lower the cost of goods. Here, we demonstrate that the bacterium Caulobacter crescentus and its highly expressed surface-layer (S-layer) protein can provide this antibody display platform. Caulobacters displaying protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific antibodies and demonstrated functional neutralization. Compared to soluble antibodies, a neutralizing anti-HIV antibody displayed on Caulobacter was as effective or more effective at neutralizing diverse HIV-1 isolates. Moreover, when an antibody reactive with an epitope induced by CD4 binding (CD4i) was codisplayed with CD4, there was significant enhancement in HIV-1 neutralization. These results suggest that caulobacters displaying anti-HIV antibodies offer a distinct improvement in the use of antibodies as microbicides. Furthermore, these reagents can specifically evaluate anti-HIV antibodies in concert with other HIV-1 blocking agents to assess the most suitable tools for conversion to scFvs, allowing for direct display within the S-layer protein and further reducing cost of goods. In summary, C. crescentus, which can be easily produced and chemically stabilized at low cost, is well suited for engineering as an effective platform, offering an inexpensive way to produce and deliver HIV-1-specific microbicides.

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Preclinical evaluation of anti-HIV microbicide products: New models and biomarkers

Cited by 43 publications

References 79 publications

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides

Enhanced Neutralization of HIV by Antibodies Displayed on the S-Layer of Caulobacter crescentus

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