Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge
Ebola virus (EBOV) is one of three filovirus members of the <i>Orthoebolavirus</i> genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifica...
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2024-10-01
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| author | Olivier Escaffre Terry L. Juelich Jennifer K. Smith Lihong Zhang Madison Pearson Nigel Bourne Alexander N. Freiberg |
| author_facet | Olivier Escaffre Terry L. Juelich Jennifer K. Smith Lihong Zhang Madison Pearson Nigel Bourne Alexander N. Freiberg |
| author_sort | Olivier Escaffre |
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| description | Ebola virus (EBOV) is one of three filovirus members of the <i>Orthoebolavirus</i> genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR<sup>−/−</sup>) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR<sup>−/−</sup> mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans. |
| format | Article |
| id | doaj-art-ae48a135c01347c19e8dd0732d709bcb |
| institution | OA Journals |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Viruses |
| spelling | doaj-art-ae48a135c01347c19e8dd0732d709bcb2025-08-20T02:04:44ZengMDPI AGViruses1999-49152024-10-011611169310.3390/v16111693Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus ChallengeOlivier Escaffre0Terry L. Juelich1Jennifer K. Smith2Lihong Zhang3Madison Pearson4Nigel Bourne5Alexander N. Freiberg6Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USAInstitute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USAInstitute for Human Infections & Immunity and Sealy & Smith Foundation, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USAEbola virus (EBOV) is one of three filovirus members of the <i>Orthoebolavirus</i> genus that can cause severe Ebola disease (EBOD) in humans. Transmission predominantly occurs from spillover events from wildlife but has also happened between humans with infected bodily fluids. Specifically, the sexual route through infectious male survivors could be the origin of flare up events leading to the deaths of multiple women. More studies are needed to comprehend this route of infection which has recently received more focus. The use of microbicides prior to intercourse is of interest if neither of the Ebola vaccines are an option. These experimental products have been used against sexually transmitted diseases, and recently polyphenylene carboxymethylene (PPCM) showed efficacy against EBOV in vitro. Shortly after, the first animal model of EBOV sexual transmission was established using type I interferon receptors (IFNAR<sup>−/−</sup>) knockout female mice in which mortality endpoint could be achieved. Here, we investigated PPCM efficacy against a mouse-adapted (ma)EBOV isolate in IFNAR<sup>−/−</sup> mice and demonstrated that 4% PPCM gel caused a 20% reduction in mortality in two distinct groups compared to control groups when inoculated prior to virus challenge. Among animals that succumbed to disease despite PPCM treatment, we report an increase in median survival time as well as a less infectious virus, and fewer virus positive vaginal swabs compared to those from vehicle-treated animals, altogether indicating the beneficial effect of using PPCM prior to exposure. A post-study analysis of the different gel formulations tested indicated that buffering the gels would have prevented an increase in acidity seen only in vehicles, suggesting that PPCM antiviral efficacy against EBOV was suboptimal in our experimental set-up. These results are encouraging and warrant further studies using optimized stable formulations with the goal of providing additional safe protective countermeasures from sexual transmission of EBOV in humans.https://www.mdpi.com/1999-4915/16/11/1693Ebola virusmicrobicidePPCMsexual transmissionintravaginal infectionIFNAR<sup>−/−</sup> mice |
| spellingShingle | Olivier Escaffre Terry L. Juelich Jennifer K. Smith Lihong Zhang Madison Pearson Nigel Bourne Alexander N. Freiberg Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge Viruses Ebola virus microbicide PPCM sexual transmission intravaginal infection IFNAR<sup>−/−</sup> mice |
| title | Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge |
| title_full | Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge |
| title_fullStr | Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge |
| title_full_unstemmed | Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge |
| title_short | Efficacy of Polyphenylene Carboxymethylene (PPCM) Gel at Protecting Type I Interferon Receptors Knockout Mice from Intravaginal Ebola Virus Challenge |
| title_sort | efficacy of polyphenylene carboxymethylene ppcm gel at protecting type i interferon receptors knockout mice from intravaginal ebola virus challenge |
| topic | Ebola virus microbicide PPCM sexual transmission intravaginal infection IFNAR<sup>−/−</sup> mice |
| url | https://www.mdpi.com/1999-4915/16/11/1693 |
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