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)m(o/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-I ocular challenge. Results. Unvaccinated A(beta)(o/o) and beta(2)m(o/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)m(o/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-l 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)m(o/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.