A Herpes Simplex Virus (HSV)-2 Single-Cycle Candidate Vaccine Deleted in Glycoprotein D Protects Male Mice From Lethal Skin Challenge With Clinical Isolates of HSV-1 and HSV-2.

Herpes simplex virus (HSV) infections manifest as recurrent oral or genital mucosal lesions, meningoencephalitis, corneal blindness, and perinatal disease. Subunit vaccines have advanced into the clinic without success. None were tested preclinically in male mice.

HSV-2 ΔgD elicits FcγR-effector antibodies that protect against clinical isolates.

A single-cycle herpes simplex virus (HSV) deleted in glycoprotein D (ΔgD-2) elicited high titer HSV-specific antibodies (Abs) that (i) were rapidly transported into the vaginal mucosa; (ii) elicited antibody-dependent cell-mediated cytotoxicity but little neutralization; (iii) provided complete protection against lethal intravaginal challenge; and (iv) prevented establishment of latency in mice. However, clinical isolates may differ antigenically and impact vaccine efficacy. To determine the breadth and further define mechanisms of protection of this vaccine candidate, we tested ΔgD-2 against a panel of clinical isolates in a murine skin challenge model.