Robust local immune response to vaccination with a live-attenuated HSV-1 strain (HSV-1 0ΔNLS) is delayed in mice vaccinated with the parental live virus

Abstract

Abstract We have identified a highly efficacious vaccine 0ΔNLS (deficient in the nuclear location signal of ICP0) against herpes simplex virus type 1 (HSV-1) using an experimental ocular mouse model. In this study, a side-by-side analysis of the host immune response was conducted at the site of vaccination (footpad, FP) and the draining (popliteal) lymph node (PLN) of mice vaccinated with 0ΔNLS versus the parental, wild type HSV-1. Both viruses replicated locally with near equal efficiency through day 3 post infection (PI). By day 5 PI, 0ΔNLS titers recovered from the FP of mice were significantly reduced in comparison to the parental virus and this reduction carried through to clearance by day 9 PI. Even though viral titers were equivalent early post vaccination, 0ΔNLS vaccinated mice generated a more robust localized immune response in the FP in terms of a noticeable increase in the infiltration of myeloid cells and an increase in select cytokines/chemokines including G-CSF, CXCL1, CXCL9, CXCL10, CCL2, CCL5, IL-6, and TNF-α. However, at later time points (days 3–7 PI) the levels of select cytokines/chemokines were elevated in the wild type virus-infected FP with a significant drop in levels from the 0ΔNLS-infected FP. A similar profile was found in the PLN as that reported in the FP. In addition, there were significantly more germinal center B cells (CD19+GL-7+CD95+) and B cells that had undergone isotype switching in the PLN of 0ΔNLS vaccinated mice compared to mice vaccinated with wild type virus by day 7 PI. Collectively, there are unique differences in the host innate and adaptive immune response comparing mice vaccinated with the 0ΔNLS vaccine compared to those exposed to parental wild type virus that continues to be studied in this lab.