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Experimental keratitis in rabbits by human HSV-1 variants: prevention and treatment
R Manservigi1, C Incorvaia, D Di Luca
1Institute of Microbiology, University of Ferrara, Italy.
Abstract:
The efficacy of different therapies and vaccine preparations was assessed for treating or preventing herpetic ocular keratitis induced by experimental inoculation in rabbits with two HSV-1 variants that display different pathogenetic potential. Early administration of acyclovir (ACV) promoted fast healing and prevented neurologic involvements: alpha-interferon (alpha-IFN) was less efficient than ACV; combined therapy with both drugs increased the antiviral effects. In an attempt to prevent the disease, rabbits were vaccinated with a slightly pathogenic HSV-1 variant or with a secreted form of an engineered HSV-1 glycoprotein gB (gB-1s) and were subsequently challenged with a highly pathogenic HSV-1 variant. Immunization of rabbits with gB-1s was much more efficient than immunization with live virus in reducing the severity of herpetic keratitis and in preventing CNS disease.
Insights
Early acyclovir (ACV) treatment effectively healed herpetic ocular keratitis in rabbits. Vaccination with engineered glycoprotein gB-1s offered superior protection against severe disease compared to live virus vaccines.
Area of Science:
- Ophthalmology
- Virology
- Immunology
Background:
- Herpetic ocular keratitis, caused by Herpes Simplex Virus type 1 (HSV-1), poses a significant threat to vision.
- HSV-1 exhibits varying pathogenetic potentials, complicating treatment and prevention strategies.
Purpose of the Study:
- To evaluate the efficacy of different therapeutic agents and vaccine candidates for treating and preventing experimental HSV-1 ocular keratitis.
- To compare the protective effects of a novel engineered glycoprotein vaccine against a live attenuated virus vaccine.
Main Methods:
- Rabbits were experimentally inoculated with two HSV-1 variants of differing pathogenicity.
- Therapeutic efficacy was assessed using acyclovir (ACV) and alpha-interferon (alpha-IFN), alone and in combination.
- Preventive efficacy was evaluated by vaccinating rabbits with a live, low-pathogenicity HSV-1 strain or an engineered secreted glycoprotein gB-1s before challenge with a high-pathogenicity HSV-1 strain.
Main Results:
- Early ACV administration accelerated healing and prevented neurological complications.
- Alpha-interferon (alpha-IFN) showed less efficacy than ACV, but combined therapy enhanced antiviral effects.
- Vaccination with gB-1s was significantly more effective than live virus immunization in reducing keratitis severity and preventing central nervous system (CNS) disease.
Conclusions:
- Early antiviral therapy with ACV is crucial for managing herpetic ocular keratitis.
- The engineered glycoprotein gB-1s represents a promising vaccine candidate for preventing severe HSV-1 ocular infections and associated neurological complications.