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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/226 |
| _version_ | 1797618807443816448 |
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| author | Tibor Bakacs Volker Sandig Imre Kovesdi |
| author_facet | Tibor Bakacs Volker Sandig Imre Kovesdi |
| author_sort | Tibor Bakacs |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:17:47Z |
| format | Article |
| id | doaj.art-4ac4f9e8ae654d7f8c5e6821954bc7fd |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:17:47Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-4ac4f9e8ae654d7f8c5e6821954bc7fd2023-11-16T22:36:44ZengMDPI AGPharmaceuticals1424-82472023-02-0116222610.3390/ph16020226Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and AcyclovirTibor Bakacs0Volker Sandig1Imre Kovesdi2Department of Probability, Alfred Renyi Institute of Mathematics, The Eotvos Lorand Research Network (ELKH), 1053 Budapest, HungaryProBioGen AG, 13086 Berlin, GermanyUnleash Immuno Oncolytics Inc., St. Louis, MO 63110, USAPractically 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.https://www.mdpi.com/1424-8247/16/2/226herpesshinglesherpes zoster ophtalmicusacyclovirinfectious bursal disease virusIBDV |
| spellingShingle | Tibor Bakacs Volker Sandig Imre Kovesdi Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir Pharmaceuticals herpes shingles herpes zoster ophtalmicus acyclovir infectious bursal disease virus IBDV |
| 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 | herpes shingles herpes zoster ophtalmicus acyclovir infectious bursal disease virus IBDV |
| url | https://www.mdpi.com/1424-8247/16/2/226 |
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