Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?

Abstract

The successful human papillomavirus and hepatitis B virus subunit vaccines contain single viral proteins that represent 22 and 12%, respectively, of the antigens encoded by these tiny viruses. The herpes simplex virus 2 (HSV-2) genome is >20 times larger. Thus, a single protein subunit represents 1% of HSV-2's total antigenic breadth. Antigenic breadth may explain why HSV-2 glycoprotein subunit vaccines have failed in clinical trials, and why live HSV-2 vaccines that express 99% of HSV-2's proteome may be more effective. I review the mounting evidence that live HSV-2 vaccines offer a greater opportunity to stop the spread of genital herpes, and I consider the unfounded 'safety concerns' that have kept live HSV-2 vaccines out of U.S. clinical trials for 25 years.

Keywords: alum + monophosphoryl lipid A adjuvant; antigenic breadth; deletion of ICP0’s nuclear localization signal; glycoprotein D; herpes simplex virus 2; infected cell protein 0; live HSV-2 vaccine; plaque-forming unit; severe-combined immunodeficiency.