Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine

Abstract

Background: Protection against herpes zoster (HZ) induced by the live attenuated zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL recipients and ZVL-naive individuals (HZ-NonVac).

Methods: In an open-label, multicenter study, adults ≥65 years of age, vaccinated with ZVL ≥5 years previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac). Participants received 2 doses of HZ/su 2 months apart. The primary objective of noninferiority of the humoral immune response 1 month post-dose 2 was considered demonstrated if the upper limit of the 95% confidence interval (CI) of the adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ-NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity, and safety were also assessed.

Results: In 430 participants, humoral immune response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and safety appeared to be comparable between groups. HZ/su was well-tolerated, with no safety concerns raised within 1 month post-dose 2.

Conclusions: HZ/su induces a strong immune response irrespective of prior vaccination with ZVL, and may be an attractive option to revaccinate prior ZVL recipients.

Clinical trials registration: NCT02581410.

Keywords: HZ/su adjuvanted herpes zoster subunit vaccine; herpes zoster; immune response; live attenuated zoster vaccine Zostavax; revaccination.

Figure 1.

Study design. Before the first participant was vaccinated, potential participants were screened for eligibility and matching purposes. Matched participants were included in the study. During the active phase of the study, participants visited the study center at specified timepoints for a blood draw to determine immune parameters (months 0, 1, and 3), and to receive the study vaccine (months 0 and 2). Only data collected during the active phase of the study are reported in this manuscript. The safety follow-up was expected to continue until August 2017. During this safety follow-up, participants are being followed for safety through monthly phone calls. A final blood draw is scheduled to take place at 12 months after the second dose of study vaccine. Abbreviations: HZ-NonVac, participants who never received the live attenuated zoster vaccine; HZ-PreVac, participants who received the live attenuated zoster vaccine ≥5 years prior to study start; HZ/su, herpes zoster subunit candidate vaccine.

Figure 2.

Participant disposition. Potential participants were first screened and matching variables were collected (see Figure 1). Only matched participants were vaccinated with herpes zoster subunit candidate vaccine (see Supplementary Table 1 for additional information on matching). Abbreviations: HZ-NonVac, participants who never received the live attenuated zoster vaccine; HZ-PreVac, participants who received live attenuated zoster vaccine ≥5 years prior to study start; SAE, serious adverse event.

Figure 3.

Humoral and cellular immune response to herpes zoster subunit candidate vaccine (HZ/su) (according to protocol cohort for immunogenicity). A, Humoral immune response to HZ/su vaccination. Anti–glycoprotein E (gE) antibody concentrations were determined by enzyme-linked immunosorbent assay. Data are geometric mean concentrations (GMCs [mIU/mL]) and error bars indicate 95% confidence intervals. B, Cellular immune response to HZ/su vaccination. The gE-specific CD4⁺ cells expressing at least 2 activation markers (CD4²⁺) were determined by intracellular staining and flow cytometry. Data are median cell counts per 10⁶ total peripheral blood mononuclear cells. Light bars indicate participants who received the live attenuated zoster vaccine ≥5 years prior to study start (HZ-PreVac group); dark bars indicate participants who never received the live attenuated zoster vaccine (HZ-NonVac group). Abbreviations: M0 = pre vaccination; M1, one month post-dose 1; M3, one month post-dose 2.

Figure 4.

Solicited adverse events (AEs) after vaccination doses (total vaccinated cohort). A, Percentage of participants reporting local solicited AEs after herpes zoster subunit candidate vaccine (HZ/su) dose 1. B, Percentage of participants reporting local solicited AEs after HZ/su dose 2. C, Percentage of participants reporting related systemic solicited AEs after HZ/su dose 1. D, Percentage of participants reporting related systemic solicited AEs after HZ/su dose 2. Light bars indicate participants who received the live attenuated zoster vaccine ≥5 years prior to study start (HZ-PreVac group); dark bars indicate participants who never received the live attenuated zoster vaccine (HZ-NonVac group). Striped sections indicate grade 3 solicited AEs. Error bars indicate 95% confidence intervals.