RVx101-vaccinated mice display minimal corneal inflammation that correlates with the absence of virus replication and preservation of peripheral vision following corneal HSV-1 challenge in mice

Abstract

Purpose : We have previously reported that HSV-1 0dNLS is a highly efficacious prophylactic vaccine against subsequent HSV-1 challenge through humoral and cell-mediated immune pathways. The current study was undertaken to evaluate the local immune response and control of virus replication and spread and correlate these results to ophthalmologic assessment of the visual axis including cornea edema and potential changes to peripheral vision using the R&D-generated virus referred to as RVx101 (termed HSV-1 0dNLS in previous publications).

Methods : C57BL/6J male and female mice were vaccinated with vehicle (phosphate buffered saline, PBS) or RVx101 (10⁴ plaque forming units, PFU) in the footpad followed by a boost (10⁴ PFU) in the ipsilateral flank 21 days later. Vaccinated mice were then subjected to ocular HSV-1 challenge with 1x10⁵ PFU HSV-1 McKrae strain. HSV-1 lytic gene expression and cytokine/chemokine content within tissue was assessed by real time RT-PCR and multiplex suspension array, respectively at day 7 post infection (PI). Cornea edema was measured by spectral domain-optical coherence tomography (SD-OCT) over 21 days PI. Peripheral vision was assessed using optokinetic tracking (OKT) responses over 21 days PI. Data was analyzed for significance (p<.05) as determined by the Holm-Sidak multi-T-test method.

Results : RVx101 vaccinated mice expressed significantly lower to no detectable HSV-1 lytic genes in the cornea and trigeminal ganglion (TG) at day7 PI compared to vehicle-vaccinated mice. This was associated with a dramatic reduction to basal levels in the protein content of several cytokines/chemokines in the cornea, TG, and circulation including GM-CSF, IFN-γ, IL-1α, IL-6, IL-9, IL-10, CXCL1, CXCL2, CXCL10, CCL2, CCL3, CCL4, and/or TNF-α. SD-OCT results showed little to no cornea edema over the 21-day PI window of assessment in the RVx101-vaccinated mice compared to a time-dependent increase in edema in the vehicle-vaccinated group. Likewise, automated OKT responses demonstrated RVx101-vaccinated animals showed no loss in peripheral vision whereas the vehicle-vaccinated controls were severely compromised to blindness.

Conclusions : RVx101 is a highly efficacious prophylactic vaccine that enhances resistance to ocular HSV-1 challenge without diminishing corneal integrity and peripheral vision.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.