No Consistent Evidence of Decreased Exposure to Varicella-Zoster Virus Among Older Adults in Countries with Universal Varicella Vaccination

Abstract

Background: Universal varicella vaccination might reduce opportunities for varicella-zoster virus (VZV) exposure and protective immunological boosting, thus increasing herpes zoster incidence in latently infected adults. We assessed humoral and cell-mediated immunity (CMI), as markers of VZV exposure, in adults aged ≥50 years.

Methods: We repurposed data from placebo recipients in a large multinational clinical trial (ZOE-50). Countries were clustered based on their varicella vaccination program characteristics, as having high, moderate, or low VZV circulation. Anti-VZV antibody geometric mean concentrations, median frequencies of VZV-specific CD4 T cells, and percentages of individuals with increases in VZV-specific CD4 T-cell frequencies were compared across countries and clusters. Sensitivity analyses using a variable number of time points and different thresholds were performed for CMI data.

Results: VZV-specific humoral immunity from 17 countries (12 high, 2 moderate, 3 low circulation) varied significantly between countries (P < .0001) but not by VZV circulation. No significant differences were identified in VZV-specific CMI between participants from 2 high versus 1 low circulation country. In 3/5 sensitivity analyses, increases in CMI were more frequent in high VZV circulation countries (.03 ≤ P < .05).

Conclusions: We found no consistent evidence of reduced VZV exposure among older adults in countries with universal varicella vaccination.

Clinical trials registration: NCT01165177.

Keywords: boosting; exposure; herpes zoster; varicella vaccine.

© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.

Grouping of countries according to their estimated VZV circulation level. Low, low VZV circulation: countries with a well-established 2-dose pediatric universal VV program. Moderate, moderate VZV circulation: countries with a well-established 1-dose pediatric universal VV program. High, high VZV circulation; countries where VV was not included in the national immunization program, the immunization program was immature or has suffered significant interruptions over time. ∗High coverage centers were excluded. Abbreviations: NA, not applicable; VV, varicella vaccination; VZV, varicella-zoster virus.

Figure 2.

VZV-induced humoral responses across time by country (adapted per-protocol cohort for humoral immunity). Results from each participant were treated as a unit. Abbreviations: CI, confidence interval; N, number of participants; VZV, varicella-zoster virus.

Figure 3.

VZV-induced humoral immune responses by countries clustered according to VZV circulation (adapted per-protocol cohort for humoral immunity). Abbreviations: CI, confidence interval; M, month; N, number of participants; VZV, varicella-zoster virus.

Figure 4.

Descriptive statistic of the frequencies of VZV-specific CD4IFN-γ+(+) T cells by country and time point (adapted per-protocol cohort for cell-mediated immunity). Abbreviations: IFN-γ, interferon-γ; M, month; N, number of participants with available results; VZV, varicella-zoster virus.

Figure 5.

Cell-Mediated Immunity Increase Analysis (Bold) and Sensitivity Analyses in Participants With Results Available for ≥2, First 4, and All 5 Time Points (Adapted Per-Protocol Cohort for Cell-Mediated Immunogenicity). Blue box/dark gray box (print version), high varicella-zoster virus circulation; Green box/light gray box (print version), low varicella-zoster virus circulation. P values were obtained using a 2-sided Fisher exact test; as the cell-mediated immunity increase analysis was descriptive, P values can be regarded as inconclusive. Abbreviations: CI, confidence interval; n (%), number (%) of patients in a given category; N, number of participants with available results.