About one-third of the US population will develop herpes zoster (HZ, commonly 
known as shingles) over a lifetime, while two-thirds will not. It is not clear 
exactly why certain people are susceptible to HZ; however, we may be coming 
closer to an answer. In this issue of the JCI, a study by Levin et al. provides 
important details concerning pathogenesis of and protection from HZ. The authors 
characterized differences in the immunologic responses induced by two HZ 
vaccines, the live attenuated zoster vaccine (ZV) and the more recently 
developed adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit 
herpes zoster vaccine (HZ/su), in vaccine-naive subjects and those previously 
vaccinated with HZ. The observed differences in responses paralleled the 
observed clinical protection of the two zoster vaccines, with HZ/su being 
superior to HZ. Together, these results seem to explain immunologically why the 
new subunit vaccine outperforms the live vaccine. These differences may also 
provide clues as to why HZ develops in the first place.