The role of neutralizing antibody and T‐helper subtypes in protection and pathogenesis of vaccinated mice following ocular HSV‐1 challenge

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Abstract
In order to determine the possible correlation of specific immune responses with protection against mortality and ocular disease following ocular herpes simplex virus type 1 (HSV‐1) challenge, BALB/c mice were vaccinated with different doses and regimens of baculovirus‐expressed gD. Neutralizing antibody, virus titres in the eyes, corneal scarring, and survival were measured. In addition, infiltration into the cornea of CD4+ T cells and cells containing the lymphokines interleukin‐2 (IL‐2), IL‐4, IL‐6 and tumour necrosis factor‐α (TNF‐α) were monitored on days 3, 7, 10, 14 and 21 post‐challenge by immunocytochemistry. The vaccination regimens used induced varying degrees of immune responses and protection upon ocular challenge with HSV‐1. Our results suggest that neutralizing antibody was the most important immune response in protecting mice against lethal ocular challenge and corneal scarring. TNF‐α and IL‐2 were not crucial in terms of survival and corneal scarring, since gD1 (one vaccination with 1 μg of gD) and gD0.1 (one vaccination with 0·1 μg of gD), both of which provided high levels of protection, showed no TNF‐α or IL‐2 expression. However, TNF‐α and IL‐2 were crucial in terms of virus clearance from the eyes, since gD3 (three vaccinations with 1 μg of gD), which had less virus in their eyes, had high numbers of TNF‐α and IL‐2 infiltrates. Finally, mock‐vaccinated mice were not protected from death and corneal disease following HSV‐1 challenge. Eyes of mock‐vaccinated mice had little or no TNF‐α or IL‐2 responses and the strongest IL‐4 and IL‐6 responses.

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