Immunotherapy of chronic viral diseases with vaccines is an important but unproven concept. We investigated the effect of a vaccine containing recombinant glycoprotein D (gD2) of herpes simplex virus type 2 (HSV-2) on the frequency of symptomatic outbreaks in patients with genital herpes. 98 patients with documented genital herpes who reported 4-14 recurrences per year were enrolled in a double-blind, placebo-controlled trial. Subjects received injections of either 100 μg gD2 in alum or alum alone (placebo) at 0 and 2 months, and recurrences were documented for 1 year. The vaccine was well tolerated. gD2 recipients reported fewer recurrences per month than placebo recipients (mean 0·42 [SE 0·05] vs 0·55 [0·05]; p=0·055), had fewer virologically confirmed recurrences per month (0·18 [0·03] vs 0·28 [0·03]; p=0·019), and had a lower median number of recurrences for the study year (4 [range 0-17] vs 6 [0-15]; p=0·039). Neither genital recurrence nor the placebo vaccine had any discernible effect on HSV-2-specific antibody responses, but gD2 vaccine boosted neutralising antibodies to HSV-2 fourfold and gD2-specific titres sevenfold over baseline levels.

These results inspire optimism about the potential use of vaccine for the treatment of chronic, recurring viral diseases.