Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older

Anthony L Cunningham, Thomas C Heineman, Himal Lal, Olivier Godeaux, Roman Chlibek, Shinn-Jang Hwang, Janet E McElhaney, Timo Vesikari, Charles Andrews, Won Suk Choi, Meral Esen, Hideyuki Ikematsu, Martina Kovac Choma, Karlis Pauksens, Stéphanie Ravault, Bruno Salaun, Tino F Schwarz, Jan Smetana, Carline Vanden Abeele, Peter Van den Steen, Ilse Vastiau, Lily Yin Weckx, Myron J Levin, ZOE-50/70 Study Group, Anthony L Cunningham, Thomas C Heineman, Himal Lal, Olivier Godeaux, Roman Chlibek, Shinn-Jang Hwang, Janet E McElhaney, Timo Vesikari, Charles Andrews, Won Suk Choi, Meral Esen, Hideyuki Ikematsu, Martina Kovac Choma, Karlis Pauksens, Stéphanie Ravault, Bruno Salaun, Tino F Schwarz, Jan Smetana, Carline Vanden Abeele, Peter Van den Steen, Ilse Vastiau, Lily Yin Weckx, Myron J Levin, ZOE-50/70 Study Group

Abstract

Background: The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials.

Methods: Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity.

Results: After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups.

Conclusions: Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination.

Clinical trials registration: NCT01165177; NCT01165229.

Figures

Figure 1.
Figure 1.
Disposition of study participants in ZOE-50/ZOE-70, zoster efficacy studies in participants ≥50 and ≥70 years of age (trial registration numbers NCT01165177 and NCT01165229). Abbreviations: ATP, according-to-protocol; HZ/su, herpes zoster subunit vaccine; mo, month; TVC, total vaccinated cohort; VE, vaccine efficacy. * details for study exclusion presented elsewhere [3, 4]. ** only participants from the ZOE-50 clinical trial were selected for inclusion in the subset for cell-mediated immunogenicity.
Figure 2.
Figure 2.
Herpes zoster subunit vaccine (HZ/su)-induced antiglycoprotein E antibody responses (according-to-protocol cohort for humoral immunogenicity): percentage of responders overall (A), the percentage of responders by age (B), geometric mean concentration (GMCs) overall (C), GMCs by age (D). Abbreviations: mo, month; N, number of participants with available results; YOA, years of age. Error bars depict 95% confidence intervals.
Figure 3.
Figure 3.
Herpes zoster subunit vaccine (HZ/su)-induced glycoprotein E-specific cell-mediated immunity (according-to-protocol cohort for cell-mediated immunogenicity): percentage of responders overall (A), percentage of responder by age (B), CD42+ frequencies overall (C), CD42+ frequencies by age (D). Only HZ/su is shown is panels C and D. Abbreviations: mo, month; N, number of participants with available results; YOA, years of age. Error bars depict 95% confidence intervals (A and B) or minimum and maximum values (C and D).
Figure 4.
Figure 4.
Frequency of CD4+ T cells expressing any combination of immune markers (according-to-protocol cohort for cell-mediated immunogenicity): polyfunctional CD4+ T-cell frequencies overall (A), polyfunctionality proportions by age group (B), and activation marker combinations overall (C). Abbreviations: mo, month; YOA, years of age. Immune markers: IFN-γ, interferon-γ; IL-2, interleukin-2; TNF-α, tumor necrosis factor-α; CD40L, cluster of differentiation 40 ligand. B shows mean percentages. Error bars in C depict interquartile ranges.

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