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 compl ex (MHC) class-I versus MHC class-II immune responses in protecting na ive 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 effectiv ely CD8(+) T cells negative, were either vaccinated or mock-vaccinated and examined for their ability to withstand HSV-I ocular challenge. R esults. Unvaccinated A(beta)(o/o) and beta(2)m(o/o) mice were both mor e susceptible to lethal ocular HSV-1 infection than the parental wild type C57BL/6J mice, indicating that both MHC-I and MHC-II were require d for optimal protection of naive mice against ocular HSV-1 challenge. Vaccinated beta(2)m(o/o) mice produced significant neutralizing antib ody 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 vacci nation 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 pr otection against death and corneal scarring. Conclusions. Passive anti body transfer, but not vaccination, protected A(beta)(o/o) mice agains t 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 o nly sufficient, but it is also required, that the vaccine induce an ef fective neutralizing antibody response.