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

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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°/° (MHC I–) and Ab°/° (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), Ab°/° (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°/° (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 2×107 plaque‐forming units (PFU) of HSV‐1. The live virus vaccine and the 7gPs vaccine also protected 80% of the β2m°/° mice against the same lethal HSV‐1 challenge dose. In contrast, in Ab°/° mice, none of the vaccines provided significant protection against the same lethal challenge dose of HSV‐1. However, at a lower challenge dose of 2×106 PFU, all three vaccines protected 70–80% of the vaccinated Ab°/° mice (compared to only 10% survival in mock vaccinated controls). Thus, vaccination provided some protection against lethal HSV‐1 challenge in both β2m°/° and Ab°/° mice; however, the protection was less than that seen in the parental C57BL/6 mice. In addition, Ab°/° mice were less well protected by vaccination than were β2m°/° mice. Our results suggest that (1) both MHC‐I and 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 important than the MHC‐I‐dependent immune response for vaccine efficacy against HSV‐1 challenge.

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