The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over...

Area of Science:

• Ophthalmology
• Virology
• Immunology

Background:

• Vaccine efficacy is typically measured by host resistance to viral challenge, reduced viral replication, and minimized pathology.
• The duration of protective immune response is critical for evaluating vaccine effectiveness and vaccination schedules.
• Herpes simplex virus type 1 (HSV-1) ocular infections can lead to significant visual impairment.

Purpose of the Study:

• To assess the long-term durability of two related vaccines, 0∆NLS and 0∆RING, against ocular HSV-1 challenge in a mouse model.
• To compare the short-term (30 days) and long-term (1 year) efficacy of these vaccines.
• To evaluate the impact of vaccination on viral control, host survival, and ocular tissue pathology.

Main Methods:

• Mice were vaccinated with either 0∆NLS or 0∆RING vaccine, or a vehicle control, followed by a prime-boost regimen.
• Ocular challenge with HSV-1 was administered, and animals were monitored for survival and viral shedding.
• Viral loads in the nervous system and cornea were quantified, along with assessments of corneal opacity, neovascularization, blink response, and visual acuity.

Main Results:

• Short-term studies showed both 0∆NLS and 0∆RING vaccines were effective in controlling viral replication and preserving the visual axis.
• Long-term assessment revealed that while vaccinated mice showed improved survival and reduced viral shedding compared to controls, functional outcomes were impaired.
• 0∆NLS vaccination led to lower viral loads in the nervous system, but corneal neovascularization and opacity were similar across all groups; functional measures like blink response and visual acuity decreased significantly post-infection.

Conclusions:

• A dichotomy exists between the development of resistance to HSV-1 infection and the preservation of functional visual performance following vaccination.
• The long-term efficacy of the evaluated vaccines against ocular HSV-1 challenge is limited, showing a decline in functional outcomes compared to short-term assessments.
• Conventional prime-boost vaccination protocols may not fully translate into sustained functional protection against ocular HSV-1 infection.