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Preventive Effect of Local Plasmid DNA Vaccine Encoding gD or gD-IL-2 on Herpetic Keratitis

¹ From the Department of Ophthalmology, Osaka University Medical School; the ² Department of Ophthalmology, Kinki University School of Medicine, Osaka; ³ Biotechnology Research Laboratories, Research and Development Division, Takeda Chemical Industries, Osaka; and the ⁴ Kobe Institute of Health, Hyogo, Japan.

PURPOSE. The goal of this study was to evaluate the effectiveness of a local plasmid DNA vaccine encoding herpes simplex virus (HSV) type 1 glycoprotein D (gD) or gD-interleukin (IL)-2 (chimeric gene of gD and human IL-2) in preventing murine herpetic keratitis.

METHODS. Plasmids containing gD (pHSDneo1), gD-IL-2 (pHDLneo1), or vaccine vector (pHSGneo) were injected subconjunctivally with BALB/c mice on days 0 and 7 (90 µg x 2). Immunization was indicated by positive virus-neutralizing antibody titer, swollen pinna (due to delayed-type hypersensitivity [DTH] reaction), and release of ⁵¹Cr from splenic and/or local cytotoxic effector cells on day 28. In another group of the immunized mice, corneas were challenged with HSV-1 (CHR3 strain, 10 µl of 3 x 10⁶ plaque-forming units [PFU]/ml). Mice were evaluated for clinical signs of epithelial or stromal keratitis on days 1 through 8 and days 10 and 14 or measured on days 2, 4, or 6 for viral titers in the eyes, trigeminal ganglia, and brain.

RESULTS. All gD-DNA–injected mice obtained specific immunity. Furthermore, gD-IL-2-DNA elicited a higher DTH reaction and more vigorous cytotoxic effector cell activity. Stromal keratitis scores were lower for all immunized mice compared with control mice, although the difference in epithelial keratitis scores was not statistically significant. Viral titers in eyes, trigeminal ganglia, and brains were suppressed in all immunized mice.

CONCLUSIONS. Local immunization with plasmid DNA encoding gD or gD-IL-2 induces humoral and cellular immunity against HSV-1 and inhibits development of stromal keratitis. gD-IL-2 DNA induces greater cell-mediated immunity than gD DNA alone. A plasmid encoding gD-IL-2 is therefore a promising candidate for a vaccine against HSV-1.

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