A new vaccine to prevent herpes zoster.

Among persons who live until the age of 85 years, herpes zoster will develop in approximately half, with an incidence that seems to be increasing. Although the disease may be mild in healthy young adults, persons over the age of 50 years and those who are immunocompromised are more likely to have complications that include herpes zoster ophthalmicus and postherpetic neuralgia. The live attenuated herpes zoster vaccine that is licensed in the United States reduces the incidence of herpes zoster by 70% among persons between the ages of 50 and 59 years, by 64% among those between the ages of 60 and 69 years, and by 38% among those 70 years of age or older.1,2 The vaccine also reduces the incidence of postherpetic neuralgia by 66% among persons between the ages of 60 and 69 years and by 67% among those 70 years of age or older. The only frequent side effects have been injection-site reactions. Lal et al.3 now report in the Journal the results of a phase 3 trial of a herpes zoster subunit vaccine consisting of a single varicella–zoster virus (VZV) glycoprotein in an AS01B adjuvant system (called HZ/su vaccine). This vaccine, which was tested in study participants who were not immunocompromised and were 50 years of age or older, had a remarkable 97.2% efficacy in preventing herpes zoster. Unlike the live attenuated vaccine, the HZ/su vaccine had an efficacy that did not diminish with increasing age. The efficacy was 96.6% among participants between the ages of 50 and 59 years, 97.4% among those between the ages of 60 and 69 years, and 97.9% among those 70 years of age or older. The HZ/su vaccine is administered in two doses, whereas the live attenuated vaccine is given in a single dose. The HZ/su vaccine was adjuvanted with AS01B, which is currently not a licensed adjuvant. This adjuvant consists of monophosphoryl lipid A and QS21, a saponin compound, formulated with liposomes. The adjuvant activates antigen-specific CD4+ T cells and antibody.4 Cell-mediated immunity, especially production of CD4+ T cells that target VZV, is associated with protection from herpes zoster,5 whereas antibody protects against varicella.6 AS01B has been used in trials of vaccines against malaria, hepatitis B, human immunodeficiency virus (HIV), and tuberculosis.4 In the current study, the rate of solicited systemic adverse reactions was 2.2 times as high in the vaccine group as in the placebo group (66% vs. 30%),3 whereas in a study of the live attenuated vaccine, the rates of systemic adverse events were similar (25% in vaccine recipients vs. 24% in controls).1 A total of 17.0% of the recipients of the HZ/su vaccine reported grade 3 symptoms that prevented normal activities, as compared with 3.2% in the placebo group. Although many of these symptoms were related to injection-site reactions, grade 3 systemic reactions occurred in 11.4% of the vaccine recipients and 2.4% of the placebo recipients and lasted a median of 1 day. However, the rates of serious adverse reactions and potential immune-mediated diseases (a theoretical concern associated with the use of adjuvants) were similar in the two groups. Since autoimmune diseases are more common among the elderly, it will be important to follow patients receiving this adjuvanted vaccine. Aside from the apparent increase in efficacy over the live attenuated vaccine, what might be the advantages of the HZ/su vaccine? A trial is under way to compare these two vaccines for efficacy and safety (ClinicalTrials.gov number, NCT02114333). The current live attenuated vaccine is contraindicated in persons with impaired