MHC-II but not MHC-I responses are required for vaccine-induced protection against ocular challenge with HSV-1.
OBJECTIVE
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.
Ghiasi
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H
Ophthalmology Research, Cedars-Sinai Medical Center Research Institute, Los Angeles, CA 90048, USA. ghiasi@csmc.edu
Cai
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Nesburn
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Wechsler
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D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003315:Cornea / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000302:isolation & purification; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007116:Immunization, Passive; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control*; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011817:Rabbits; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage*
D000914:Antibodies, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D014765:Viral Vaccines