Microbicide research: current and future directions

Ramjee, Gita

doi:10.1097/coh.0b013e32833a9f66

Cited by 22 publications

(16 citation statements)

References 44 publications

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“…Mounting evidence indicates that cervicovaginal inflammation caused by sexually transmitted infections, bacterial vaginosis (BV), and some vaginal products, including microbicides, might increase HIV-1 infection risk (19,22,35). However, the mechanism underlying such a phenomenon is not well-known, and a validated biomarker of cervicovaginal inflammation is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…T he epidemic of human immunodeficiency virus type 1 (HIV-1), when combined with the lack of an effective vaccine, has created an urgent need for a female-controlled method to reduce the risk of HIV-1 transmission (35). Microbicides are defined as products that can be applied topically for the prevention of HIV-1 and other sexually transmitted infections by creating chemical, biological, and/or physical barriers.…”

mentioning

confidence: 99%

“…Microbicides are defined as products that can be applied topically for the prevention of HIV-1 and other sexually transmitted infections by creating chemical, biological, and/or physical barriers. As such, they may offer one of the most promising preventive interventions by their accessible cost, ready availability, wide acceptance, and female-controlled use (35). To date, seven candidate microbicides have been tested in clinical trials.…”

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confidence: 99%

“…While tenofovir showed some degree of preventive effects, the other products were shown to have no effect on HIV-1. Among them, cellulose sulfate and N9 were even shown to have a trend toward an increased risk of HIV-1 infection (1,35).…”

mentioning

confidence: 99%

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L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

Zhong

Yang

et al. 2012

Antimicrob Agents Chemother

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A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

Zhong

Yang

et al. 2012

Antimicrob Agents Chemother

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“…Taylor and Davies have nicely reviewed the pharmacology of ART [20]. Ramjee has reviewed [21] the topical use of antiretroviral agents for the same purpose. The nonspecific agents (Buffergel, PRO2000) tested have been disappointing, and future emphasis will focus on antiretroviral agents, some of which are still in development.…”

mentioning

confidence: 99%

HIV prevention 2010: where are we now and where are we going?

Cohen

Fidler

2010

Current Opinion in HIV and AIDS

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Protein and oligonucleotide delivery systems for vaginal microbicides against viral STIs

Steinbach

2014

Cell. Mol. Life Sci.

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Intravaginal delivery offers an effective option for localized, targeted, and potent microbicide delivery. However, an understanding of the physiological factors that impact intravaginal delivery must be considered to develop the next generation of microbicides. In this review, a comprehensive discussion of the opportunities and challenges of intravaginal delivery are highlighted, in the context of the intravaginal environment and currently utilized dosage forms. After a subsequent discussion of the stages of microbicide development, the intravaginal delivery of proteins and oligonucleotides is addressed, with specific application to HSV and HIV. Future directions may include the integration of more targeted delivery modalities to virus and host cells, in addition to the use of biological agents to affect specific genes and proteins involved in infection. More versatile and multipurpose solutions are envisioned that integrate new biologicals and materials into potentially synergistic combinations to achieve these goals.

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Microbicide research: current and future directions

Abstract: In the recent past, microbicide research has had disappointing outcomes. However, it has also provided a better understanding of factors that may reduce effectiveness of promising products, enabling the field to be better equipped to select and test new products.

Cited by 22 publications

References 44 publications

L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

L-Selectin and P-Selectin Are Novel Biomarkers of Cervicovaginal Inflammation for Preclinical Mucosal Safety Assessment of Anti-HIV-1 Microbicide

HIV prevention 2010: where are we now and where are we going?

Protein and oligonucleotide delivery systems for vaginal microbicides against viral STIs

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