Live Attenuated Zoster Vaccine Boosts Varicella Zoster Virus (VZV)-Specific Humoral Responses Systemically and at the Cervicovaginal Mucosa of Kenyan VZV-Seropositive Women

Abstract

Background: Attenuated varicella zoster virus (VZV) is a promising vector for recombinant vaccines. Because human immunodeficiencyvirus (HIV) vaccines are believed to require mucosal immunogenicity, we characterized mucosal VZV-specific humoral immunity following VZVOka vaccination.

Methods: Adult Kenyan VZV-seropositive women (n = 44) received a single dose of the live zoster VZVOka vaccine. The anamnestic responses to the virus were followed longitudinally in both plasma and mucosal secretions using an in-house glycoprotein enzyme-linked immunosorbent assay and safety and reactogenicity monitored. VZV seroprevalence and baseline responses to the virus were also characterized in our cohorts (n = 288).

Results: Besides boosting anti-VZV antibody responses systemically, vaccination also boosted anti-VZV immunity in the cervicovaginal mucosa with a 2.9-fold rise in immunoglobulin G (P < .0001) and 1.6-fold rise in immunoglobulin A (IgA) (P = .004) from the time before immunization and 4 weeks postvaccination. Baseline analysis demonstrated high avidity antibodies at the gastrointestinal and genital mucosa of VZV-seropositive women. Measurement of VZV-specific IgA in saliva is a sensitive tool for detecting prior VZV infection.

Conclusions: VZVOka vaccine was safe and immunogenic in VZV-seropositive adult Kenyan women. We provided compelling evidence of VZV ability to induce genital mucosa immunity.

Clinical trials registration: NCT02514018.

Figure 1.

Assessment of mucosal varicella zoster virus (VZV)–specific antibody responses in a cohort of VZV-seropositive women. A, Concentration of VZV-specific immunoglobulin G (IgG) in plasma and VZV-specific IgG and immunoglobulin A (IgA) in cervicovaginal secretions (CVS), rectal secretions (RS), and saliva from 44 VZV-seropositive women. B, Avidity index of VZV-specific IgG in plasma and CVS and of IgA in RS prior to vaccination. Graphs show median and interquartile range. Dotted lines show limit of detection (LOD).

Figure 2.

Systemic varicella zoster virus (VZV)–specific immunoglobulin G (IgG) prior to and after VZV vaccination in a cohort of VZV-seropositive women. A, Vaccination schedule and longitudinal sample collection time points used in this study. B, Concentration of VZV-specific IgG assessed longitudinally in plasma prior to and up to 48 weeks postvaccination. C, Fold change in VZV-specific IgG concentrations in relation to week 0 (baseline). Graphs show median and interquartile range. Time points were compared to week 0 using Wilcoxon signed-rank test, and adjusted for multiple comparisons using step-down procedure. *P < .05; **P < .01; ****P < .0001. Dotted line shows limit of detection (LOD).

Figure 3.

Mucosal varicella zoster virus (VZV)–specific immunoglobulin G (IgG) and/or immunoglobulin A (IgA) prior to and after VZV vaccination in a cohort of VZV-seropositive women. A, Concentration of VZV-specific IgG in cervicovaginal secretions (CVS) and of VZV-specific IgA in CVS, rectal secretion (RS), and saliva prior to and postvaccination. B, Fold-change in VZV-specific IgG concentration in CVS and of VZV-specific IgA concentration in CVS, RS, and saliva in relation to week 0. Graphs show median and interquartile range. Time points were compared to week 0 (baseline) using Wilcoxon signed-rank test, and adjusted for multiple comparisons using step-down procedure. *P < .05; **P < .01; ***P < .001; ****P < .0001. Dotted lines indicate the respective limit of detection.

Figure 4.

Correlations between the concentrations of varicella zoster virus (VZV)–specific immunoglobulin G (IgG) in plasma and VZV-specific IgG and immunoglobulin A (IgA) in mucosal secretions. A, Correlations between VZV-specific IgG levels in plasma and cervicovaginal secretion (CVS), and between VZV-specific IgG levels in plasma and VZV-specific IgA in CVS, saliva, and rectal secretions (RS). B, Correlation between the concentration of anti-VZV IgA in CVS and in the other mucosal secretions (saliva and RS) and between anti-VZV IgA and IgG in CVS. Graphs show the Spearman's correlation (r_s), degree of freedom (df), and P value.