Abstract

Abstract Using an experimental mouse model we compared the host immune response of a mutant HSV-1, termed 0ΔNLS (deficient in the nuclear location signal of ICP0), a highly efficacious prophylactic vaccine against ocular HSV-1 infection, to that of the parental HSV-1 virus, termed GFP105 (KOS background). C57BL/6 mice were infected in the footpad (FP) with 1×105 plaque forming units of virus and at times post infection (PI), organized lymphoid tissues were analyzed for changes in the immune profile. 0ΔNLS infected animals were more efficient in clearance of virus from the FP and generated a more robust chemokine responses and myeloid cell infiltration in FP at early time points (day 1–3 PI) compared to GFP105 infected mice. By day 7 PI, there were significantly more GC B cells and isotype switched B cells in the PLN of mice infected with 0ΔNLS in comparison to GFP105 infected animals. In addition, an increased number of follicular helper CD4 T cells along with enhanced IL-21 cytokine production and an increased number of antigen-specific CD8 T cells against major and sub-major HSV-1 epitopes was noted. In contrast, by day 21 PI, no difference in T cell and B cell subset was found in the PLN comparing the two groups of infected mice. Furthermore, mice which were re-exposed to 0ΔNLS 21 days PI showed an increased number of metabolically active plasma cells from the bone marrow and secretion of IgG by memory B cells after pre-activation compared to those re-infected with GFP105. In addition, an increased number of IFN-ɤ secreting, HSV-1-specific CD8 T cells from the re-exposed 0ΔNLS mice was observed as well. Collectively, these results warrant further studies to fully understand the efficacy of the 0ΔNLS virus as an effective vaccine against ocular HSV-1 infection.

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