Immune characteristics correlating with HSV‐1 immune control and effect of squaric acid dibutyl ester on immune characteristics of subjects with frequent herpes labialis episodes

INTRODUCTION: Differences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV‐1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated. METHODS: PBMCs were collected from persons positive for IgG against HSV‐1 and having frequent, infrequent, or no herpes labialis outbreaks. The PBMCs were tested for proliferation against HSV‐1 and a fungal antigen (Candida) and immune gene expression in the presence of HSV‐1 and Candida. On day 1 after blood collection the subjects with frequent outbreaks were dosed topically on the arm once with SADBE, and their PBMCs were collected and tested 8 weeks later. RESULTS: Those with good immune control of their HSV‐1 infection (fewer outbreaks) differ from those with poorer immune control in these ways: (1) Greater PBMC proliferation in vitro to HSV‐1, HSV‐1‐infected cell extracts, and Candida considered together (P < 0.01). (2) Higher expression of IFNG and five other immune‐related genes (P < 0.05 for each) and lower expression of IL5 and two other immune‐related genes (P < 0.05 for each) in PBMCs in vitro stimulated with HSV‐1 virus. The subjects with frequent outbreaks were treated once with SADBE, and 56 days later the PBMCs of these subjects differed from PBMCs from the same subjects taken on day 1 before treatment in exactly the same ways listed above as differences between those with good and poor immune control of HSV‐1, and at the same levels of significance. CONCLUSIONS: Higher IFNG and lower IL5 expression by PBMCs in the presence of HSV‐1 correlate with fewer herpes labialis outbreaks, and a single topical dose of SADBE to the arm of subjects with frequent herpes labialis episodes improves immune response to HSV‐1.