The importance of MHC-I and MHC-II responses in vaccine efficacy against lethal herpes simplex virus type 1 challenge

Abstract

To investigate the importance of major histocompatability complex (MHC) class I- and MHC class II-dependent immune responses in herpes simplex virus-1 (HSV-1) vaccine efficacy, groups of β2m(φ) (MHC-I(-)) and A(b)(φ), (MHC-II(-)) mice were inoculated with various vaccines, and then 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)(φ) (MHC-II(-)) mice developed no enzyme-linked immunosorbent assay (ELISA) or neutralizing antibody titres. In contrast, significant ELISA and neutralizing antibody titres were induced in β2m(φ) (MHC-I(-)) mice by all three vaccines. The neutralizing antibody titres were similar for all three vaccines, but were only ≃ 1/4 to 1/3 of that developed in C57BL/6 (parental) mice vaccinated with the same antigens. All three vaccines protected 100% of the wild-type C57BL/6 mice against lethal challenge with 2 x 107 plaque-forming units (PFU) of HSV-1. The live virus vaccine and the 7gPs vaccine also protected 80% of the β2m(φ) mice against the same lethal HSV-1 challenge dose. In contrast, in A(b), mice, none of the vaccines provided significant protection against the same lethal challenge dose of HSV-1. However, at a lower challenge dose of 2 X 106 PFU, all three vaccines protected 70-80% of the vaccinated A(b) mice (compared to only 10% survival in mock vaccinated controls). Thus, vaccination provided some protection against lethal HSV-1 challenge in both β2m(φ) and A(b)(φ) mice; however, the protection was less than that seen in the parental C57BL/6 mice. In addition, A(b)(φ) mice were less well protected by vaccination than were β2m(φ) mice. Our results suggest that (1) both MHC-I and MHC-II are involved in vaccine efficacy against HSV-I 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 important than the MHC-I-dependent immune response for vaccine efficacy against HSV-1 challenge.