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Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir

Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithel...

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Autores principales: Bakacs, Tibor, Sandig, Volker, Kovesdi, Imre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958712/
https://www.ncbi.nlm.nih.gov/pubmed/37259374
http://dx.doi.org/10.3390/ph16020226
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author Bakacs, Tibor
Sandig, Volker
Kovesdi, Imre
author_facet Bakacs, Tibor
Sandig, Volker
Kovesdi, Imre
author_sort Bakacs, Tibor
collection PubMed
description Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.
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spelling pubmed-99587122023-02-26 Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir Bakacs, Tibor Sandig, Volker Kovesdi, Imre Pharmaceuticals (Basel) Opinion Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed. MDPI 2023-02-01 /pmc/articles/PMC9958712/ /pubmed/37259374 http://dx.doi.org/10.3390/ph16020226 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Opinion
Bakacs, Tibor
Sandig, Volker
Kovesdi, Imre
Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title_full Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title_fullStr Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title_full_unstemmed Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title_short Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
title_sort combination therapy for the treatment of shingles with an immunostimulatory vaccine virus and acyclovir
topic Opinion
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958712/
https://www.ncbi.nlm.nih.gov/pubmed/37259374
http://dx.doi.org/10.3390/ph16020226
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