MHC-II but not MHC-I responses are required for vaccine-induced protection against ocular challenge with HSV-1

PURPOSE: To determine the importance of major histocompatibility complex (MHC) class-I versus MHC class-II immune responses in protecting naive versus vaccinated mice against an ocular HSV-1 challenge. METHODS: Class-II deficient A beta o/o (CD4-CD8+ T cells) knockout mice, which are effectively CD4+ T cells-negative, and class-I deficient beta(2)mo/o (CD4+CD8- T cells) knockout mice, which are effectively CD8+ T cells negative, were either vaccinated or mock-vaccinated and examined for their ability to withstand HSV-1 ocular challenge. RESULTS: Unvaccinated A beta o/o and beta(2)mo/o mice were both more susceptible to lethal ocular HSV-1 infection than the parental wild type C57BL/6J mice, indicating that both MHC-I and MHC-II were required for optimal protection of naive mice against ocular HSV-1 challenge. Vaccinated beta(2)mo/o mice produced significant neutralizing antibody titers, and following ocular challenge, these mice were completely protected against death and corneal scarring. In contrast, vaccinated A beta o/o mice developed no neutralizing antibody titers and vaccination did not provide these mice with any protection against death or corneal scarring. Passive transfer of anti-HSV-1 antibody into A beta o/o mice up to 6 days post ocular challenge resulted in complete protection against death and corneal scarring. CONCLUSIONS: Passive antibody transfer, but not vaccination, protected A beta o/o mice against ocular challenge. In contrast, vaccination completely protected beta(2)mo/o mice. These results suggest for a vaccine to provide optimal protection against ocular HSV-1 challenge in this system, it is not only sufficient, but it is also required, that the vaccine induce an effective neutralizing antibody response.