Previous immunization of mice with herpes simplex virus type-1 strain MP protects against secondary corneal infection.

Herpes simplex virus (HSV)-induced ocular disease is occurring in epidemic proportions throughout the world, and is the number one cause of unilateral corneal blindness in all developed countries. We have found, in a mouse model of herpes simplex keratitis (HSK), that products encoded by the Igh-1 locus on chromosome 12 exert a profound influence on the immune/inflammatory response in the cornea after HSV inoculation in the cornea. Thus, mice with Igh-1c or Igh-1d phenotype routinely develop extreme keratopathy and loss of corneal clarity after HSV encounter in the eye, while congenic strains expressing other Igh-1 phenotypes develop substantially less keratopathy. We examined the effect of previous subcutaneous immunization with the mutant, less virulent, MP strain of HSV on the development of keratitis and encephalitis after secondary corneal inoculation with strains MP, mP, F, and KOS. A/J mice (Igh-1c), 5-6 weeks old, were injected sc with live HSV-1 strain MP. Controls were injected with culture media without virus. Three weeks later both immunized and control nonimmunized animals were challenged in the cornea with HSV-1, strains MP, mP, F, and KOS. The animals were clinically scored for keratitis and encephalitis at regular intervals for 21 days following corneal challenge. None of the immunized animals challenged in the cornea with strain MP, 5 X 10(4) plaque-forming units (PFU), developed clinical signs of encephalitis compared to 86% of unimmunized controls. Of the immunized animals challenged in the cornea with strain MP, 5 X 10(4) PFU, only 18% developed a mild keratitis, while 96% of unimmunized controls developed severe keratitis. Mice immunized subcutaneously with MP and subsequently challenged corneally with other HSV-1 strains (mP, F, or KOS) were also protected from development of severe keratopathy.