THE IMPORTANCE OF MHC-I AND MHC-II RESPONSES IN VACCINE EFFICACY AGAINST LETHAL HERPES-SIMPLEX VIRUS TYPE-1 CHALLENGE

To investigate the importance of major histocompatability complex (MHC ) class I- and MHC class II-dependent immune responses in herpes simpl ex virus-1 (HSV-1) vaccine efficacy, groups of beta(2)m(%) (MHC I-) an d A(b)(%) (MHC II-) mice were inoculated with various vaccines, and th en challenged intraperitoneally with HSV-1. Following vaccination with either live avirulent HSV-1, expressed HSV-1 glycoprotein D (gD), or a mixture of seven expressed HSV-1 glycoproteins (7gPs), A(b)(%) (MHC- II-) mice developed no enzyme-linked immunosorbent assay (ELISA) or ne utralizing antibody titres. In contrast, significant ELISA and neutral izing antibody titres were induced in beta(2)m(%) (MHC-I-) mice by all three vaccines. The neutralizing antibody titres were similar for all three vaccines, but were only approximate to 1/4 to 1/3 of that devel oped in C57BL/6 (parental) mice vaccinated with the same antigens. All three vaccines protected 100% of the wild-type C57BL/6 mice against l ethal challenge with 2 x 10(7) plaque-forming units (PFU) of HSV-1. Th e live virus vaccine and the 7gPs vaccine also protected 80% of the be ta(2)m(%) mice against the same lethal HSV-1 challenge dose. In contra st, in A(b)(%) mice, none of the vaccines provided significant protect ion against the same lethal challenge dose of HSV-1. However, at a low er challenge dose of 2 x 10(6) PFU, all three vaccines protected 70-80 % of the vaccinated A(b)(%) mice (compared to only 10% survival in moc k vaccinated controls). Thus, vaccination provided some protection aga inst lethal HSV-1 challenge in both beta(2)m(%) and A(b)(%) mice; howe ver, the protection was less than that seen in the parental C57BL/6 mi ce. In addition, A(b)(%) mice were less well protected by vaccination than were beta(2)m(%) mice. Our results suggest that (1) both MHC-I an d MHC-II are involved in vaccine efficacy against HSV-1 challenge; (2) both types of responses must be present for maximum vaccine efficacy; and (3) the MHC-II-dependent immune response appeared to be more impo rtant than the MHC-I-dependent immune response for vaccine efficacy ag ainst HSV-1 challenge.