Safety and immunogenicity of a Herpes Zoster subunit vaccine in Japanese population aged ≥50 years when administered subcutaneously vs. intramuscularly

Abstract

The impact of alternate routes of vaccine administration, subcutaneous (SC) or intramuscular (IM), on the safety and immunogenicity of herpes zoster subunit candidate vaccine (HZ/su) was assessed in Japanese adults aged ≥ 50 y. During this phase III open-label study, 60 subjects were randomized (1:1) to receive HZ/su through SC or IM routes in a 0, 2 month schedule. Vaccine response rates (VRRs) and geometric mean concentrations (GMCs) of varicella zoster virus glycoprotein E (gE)-specific antibodies were determined by ELISA. Solicited and unsolicited symptoms were recorded for 7 and 30 d after each vaccination and graded 1-3 in severity. Serious adverse events (SAEs) were recorded throughout the study. At one month post-dose 2, VRRs were 100% (95% Confidence Interval (CI): 88.1-100) in both groups; anti-gE antibody GMCs were 44126.1 mIU/ml (95% CI: 36326.1-53601.0) and 45521.5 mIU/ml (95% CI; 37549.5-55185.9) in the SC and IM groups, respectively. Injection site reactions (pain, swelling and redness) were common, and observed more frequently following SC administration. Grade 3 redness and swelling were more frequently observed after SC administration. Fatigue and headache were the most frequently reported general symptoms for both routes of administration. Ten and 7 unsolicited AEs were reported in the SC and IM group, respectively. Two unsolicited AEs (1 in SC; 1 in IM) were considered related to vaccination by the investigator. Three non-fatal SAEs considered unrelated to vaccination were reported during the study. Administration of the HZ/su vaccine candidate resulted in a substantial immune response that was comparable between SC and IM subjects, but local reactogenicity may be greater for SC.

Trial registration: ClinicalTrials.gov NCT01777321.

Keywords: HZ/su vaccine; adjuvant; adjuvanted vaccine; herpes zoster; immunogenicity; intramuscular; reactogenicity; subcutaneous.

Figure 1.

Disposition of study participants. SC: Subcutaneous IM: Intramuscular.

Figure 2.

Vaccine response rate and geometric mean concentrations of anti-gE antibody (ATP cohort for immunogenicity). Samples were collected at the indicated time points (for both subcutaneous (SC) versus intramuscular (IM) groups) and anti-gE antibody concentrations were determined by ELISA. Data are vaccine response rates (VRRs) and geometric mean concentrations (GMCs) and error bars indicate 95% confidence interval.

Figure 3.

Overall occurrence of solicited injection site reactions and general symptoms during the 7-day vaccination follow-up period (Total vaccinated cohort).