Effect of herpes simplex virus-1 gD or gD-IL-2 DNA vaccine on herpetic keratitis.
OBJECTIVE
To evaluate the efficacy of DNA immunization using herpes simplex virus (HSV)-1 gD or gD-IL-2 (chimeric gene of gD and human IL-2) with reference to their immune responses and preventive effect on the development of murine herpetic stromal keratitis, based on our previous work.


METHODS
Plasmids containing gD (pHSDneol) or gD-IL-2 (pHDLneol) were constructed, and gD or gD-IL-2 peptides were purified. BALB/c mice were immunized by hypodermal injection, subconjunctival injection, or topical eye drop twice at 7-day intervals. Attained anti-HSV immune reaction was estimated, including neutralizing antibody, delayed-type hypersensitivity (DTH) measured by the swelling of the ear pinna, and cytotoxic T lymphocyte (CTL) measured by 51Cr release from MHC-matched target cells by splenic and/or local lymph node cells. The corneas of a group of the immunized mice were challenged with CHR3 strain of HSV-1 (10 microL of 3 x 10(6) PFU/mL) 3 weeks after the last immunization. Clinical signs (stromal and epithelial keratitis) were scored. Results. All gD- or gD-lL-2-immunized mice developed specific neutralizing antibody. Delayed-type hypersensitivity and CTL were obtained in gD DNA- or gD-IL-2 DNA-immunized mice. Chimeric DNA vaccine gD-IL-2 elicited higher DTH and more vigorous CTL activity. The scores of stromal keratitis for all gD- or gD-IL-2-immunized mice were significantly suppressed, although those of epithelial keratitis were not. Conclusion. Immunization with gD or gD-IL-2 was effective against herpetic stromal keratitis. By focusing specifically on high induction of cell-mediated immunity, gD-IL-2 DNA could have possible clinical applications against HSV-1 in the future.
Inoue
Tomoyuki
T
Department of Ophthalmology, Osaka University Medical School, Osaka, Japan. tinoue@virus.kyoto-u.ac.jp
Inoue
Yoshitsugu
Y
Hayashi
Kozaburo
K
Shimomura
Yoshikazu
Y
Fujisawa
Yukio
Y
Aono
Aki
A
Tano
Yasuo
Y
D000818:Animals; D003319:Corneal Stroma / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D018259:Herpesvirus 1, Human / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007114:Immunization; D007376:Interleukin-2 / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage*; D014759:Viral Envelope Proteins / Q000235:genetics*
D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1