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The successful human papillomavirus (HPV) and hepatitis B virus (HBV) subunit vaccines contain single viral proteins that represent 22% and 12%, respectively, of the total antigens encoded by these simple viruses. The herpes simplex virus 2 (HSV-2) genome is 20 and 50 times larger, respectively. Thus, single protein subunit vaccines represent only 1% of HSV-2’s total antigenic breadth. The concept of antigenic breadth offers a unifying explanation for why HSV-2 glycoprotein D subunit vaccines have repeatedly failed in human clinical trials, and why live HSV-2 vaccines that encode 99% of HSV-2’s antigens are more effective in side-by-side tests. We believe that live HSV-2 vaccines represent an unexplored opportunity to stop the genital herpes epidemic.
