A live-attenuated HSV-2 ICP0- virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine (106.22)

Abstract Many herpes simplex virus 2 (HSV-2) vaccines rely on combinations of HSV-2’s glycoprotein D (gD-2) and a potent adjuvant. The Simpilirix™ vaccine is a gD-2 subunit vaccine that recently failed in human clinical trials (Science, 2010, 330:304). We have proposed that immunization with an ICP0- mutant virus, HSV-2 0ΔNLS, would be more effective (PLoS ONE, 2010, 5:e12251). The current study was initiated to test this hypothesis. Mice immunized with a gD-2 subunit produced high titers of gD-2 antibody, but were poorly protected against HSV-2 challenge of the vagina or eyes (survival rate = 3 of 45). In contrast, 114 of 115 mice immunized with HSV-2 0ΔNLS survived the same HSV-2 challenges, and protective immunity endured for 6 months. We present several lines of evidence that immunization with HSV-2 0ΔNLS was 10- to 100-fold more protective against HSV-2 infection than a gD-2 subunit. We conclude that a gD-2 vaccine does not protect mice or humans from HSV-2 infections, and infer that live-attenuated HSV-2 would be 10 to 100 times more effective in preventing genital herpes.