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Derek J Royer, Danielle M Robertson, Joshua F Hendrix, Daniel J Carr; The HSV-1 0ΔNLS vaccine functionally preserves visual axis integrity following corneal HSV-1 challenge in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4936. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously reported that humoral immunity serves as a strong correlate of prophylactic protection against corneal herpes simplex virus (HSV-1) infection and basic ocular pathology using a live-attenuated virus termed HSV-1 0ΔNLS as a vaccine. This study investigates the contributions of cellular and innate immunity to prophylactic protection mediated by HSV-1 0ΔNLS and systematically characterizes the quality of protection afforded to the visual axis against ocular pathology.
Mice were vaccinated with HSV-1 0ΔNLS, a glycoprotein subunit vaccine (gD-2), or saline using a prime-boost regimen and subsequently challenged in the cornea with 1x104 PFU HSV-1 McKrae. Viral pathogenesis and mechanisms of immunologic protection were evaluated in HSV-1 0ΔNLS-vaccinated wild-type (WT), B cell deficient (µMT), T cell deficient (TCRα-/-), and interferon (IFNα/β) receptor deficient (Ifnar1-/-) mice on a C57BL/6 background. The protective contributions of T cells were assessed in adoptive transfer experiments. Multiple modalities were utilized to quantify visual axis health in WT mice following HSV-1 challenge. Corneal scarring and neovascularization were assessed by slit lamp, confocal, and second harmonic generation (SHG) microscopy. Corneal sensation was measured by Cochet-Bonnet esthesiometry. Optokinetic tracking reflexes were measured as a functional correlate of visual acuity.
Protection elicited by HSV-1 0ΔNLS required B cells and T cell help to generate humoral protection, but did not require IFNα/β signaling for animal survival. Adoptive transfer of T cells from vaccinated animals elicited meager protection in TCRα-/- mice, although this effect was abrogated upon neutralizing CD40L-dependent T cell help to B cells. All modalities employed to assess health of the visual axis indicate that the HSV-1 0ΔNLS vaccine provides superior protection against ocular pathology substantiated by maintenance of corneal avascularity, sensation, clarity and visual acuity following HSV-1 challenge (p <0.001 by ANOVA for all metrics relative to naive or gD-2 immunized controls; data reflect multiple independent experiments).
These findings further support the protective contributions of humoral immunity to prophylactic protection against ocular HSV-1 infection using quantitative metrics of ocular pathology.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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