Shingrix glycoprotein E antigen antibody response duration of protection

Shingrix anti-glycoprotein E antibody responses plateau at 5-7 fold above baseline levels by year 3 and persist for at least 10-11 years post-vaccination.

Abstract

Shingrix (adjuvanted recombinant zoster vaccine, RZV) elicits anti-glycoprotein E antibody responses that persist for at least 10-11 years post-vaccination. Across 10 studies with follow-up ranging from 12 months to 11 years, anti-gE antibody concentrations demonstrated a consistent pattern: an initial peak at one month post-dose 2 (17,000-19,000 mIU/mL), followed by a decline that plateaued around year 3 at 5- to 7-fold above pre-vaccination baseline levels. This plateau persisted through at least 12 years of follow-up, with antibody levels never returning to baseline. Vaccine efficacy against herpes zoster remained above 84% annually through year 8, with overall efficacy estimates of 81.6-90.9% across studies with 4-10 years of follow-up. The 11-year final analysis showed overall efficacy of 87.7% (95% CI: 84.9-90.1%) from vaccination through end of follow-up, though efficacy was lower in adults ≥70 years (73.2%) compared to younger age groups (86.7-87.1%). Cell-mediated immune responses paralleled humoral immunity, plateauing at 3.3-7-fold above baseline and persisting through 10-11 years. Similar antibody response patterns were observed in general populations, Asian populations, and immunocompromised renal transplant recipients, indicating robust protection across diverse host contexts for at least a decade following vaccination.

Methods

We analyzed 10 sources from an initial pool of 200, using 8 screening criteria. Each paper was reviewed for 5 key aspects that mattered most to the research question.

Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of Semantic Scholar and OpenAlex.

Screening

We screened in sources based on their abstracts that met these criteria:

• Shingrix Vaccine: Does this study involve participants who received Shingrix (recombinant zoster vaccine)?
• Relevant Outcomes: Does this study measure glycoprotein E-specific antibody responses and/or clinical protection against herpes zoster?
• Follow-up Duration: Does this study have a follow-up duration of at least 12 months post-vaccination?
• Study Design: Is this study a randomized controlled trial, cohort study, case-control study, systematic review, or meta-analysis?
• Study Population: Does this study include adults aged 18 years and older?
• Quantitative Data: Does this study report quantitative measures of antibody levels, antibody persistence, vaccine efficacy, or effectiveness over time?
• Shingrix Focus: Does this study include Shingrix data (rather than focusing solely on live zoster vaccine/Zostavax without Shingrix comparison)?
• Human Studies: Is this a human study (not an in vitro or animal study)?

Data extraction

We asked a large language model to extract each data column below from each paper. We gave the model the extraction instructions shown below for each column.

• Study Duration:
  • Maximum follow-up time post-vaccination (in years/months)
  • Specific time points when measurements were taken (e.g., Y1, Y2, Y4, Y6, Y10)
• Anti-gE Antibody Levels:
  • Measurement method (ELISA, etc.)
  • Antibody concentration values at each time point
• Vaccine Efficacy:
  • Overall vaccine efficacy percentages with 95% confidence intervals
  • Annual vaccine efficacy estimates by year post-vaccination
• Antibody Persistence:
  • Description of antibody level changes over time
• Sample Characteristics:
  • Total number of participants in antibody analysis
  • Age range and mean age at vaccination
  • Any exclusions or dropouts affecting long-term follow-up

Results

Characteristics of included studies

The review included 10 studies evaluating the duration of protection from Shingrix (adjuvanted recombinant zoster vaccine, RZV) through anti-glycoprotein E (gE) antibody responses and vaccine efficacy. Studies varied in design, duration, and population characteristics.

Anti-glycoprotein E antibody concentrations over time

Studies consistently measured anti-gE antibody concentrations using enzyme-linked immunosorbent assay (ELISA), with a technical cutoff of 97 mIU/mL for seropositivity.

Vaccine efficacy against herpes zoster over time

Vaccine efficacy data demonstrated sustained protection across multiple years of follow-up, with annual estimates and age-stratified analyses available from several studies.

Cell-mediated immune responses

While antibody levels provide one measure of immunologic persistence, cell-mediated immunity (CMI) also contributed to sustained protection. Studies measured gE-specific CD4[2+] T-cells expressing ≥2 activation markers using intracellular cytokine staining.

The frequency of gE-specific CD4[2+] T-cells remained above baseline from year 6 to year 8 post-vaccination.

Protection in immunocompromised populations

The renal transplant study provided critical data on RZV immunogenicity in chronically immunosuppressed individuals receiving daily immunosuppressive therapy. In this population, anti-gE antibody GMCs were 1354.4 mIU/mL pre-vaccination, peaked at 19,163.8 mIU/mL (95% CI: 15,041.5-24,416.0) at 1 month post-dose 2, and remained elevated at 8545.1 mIU/mL (95% CI: 6,753.7-10,811.5) at 12 months post-dose 2. This represented a 14.1-fold increase at peak and a sustained 6.3-fold increase at 12 months post-dose 2. Both humoral and cell-mediated immune responses were higher in RZV recipients compared to placebo across all post-vaccination time points and persisted above pre-vaccination baseline at 12 months post-dose 2.

Synthesis

The data demonstrate remarkably consistent immunologic and clinical protection across diverse populations and extended follow-up periods, though with some nuanced temporal patterns that warrant interpretation.

Antibody dynamics and plateau phase: All studies converge on a characteristic antibody response pattern: an initial peak at 1 month post-dose 2 (17,000-19,000 mIU/mL), followed by a decline that stabilizes into a plateau phase beginning around year 3. This plateau represents a 5- to 7-fold elevation above baseline that persists through at least 10-12 years.

Vaccine efficacy stability with late fluctuation: Vaccine efficacy remained remarkably stable at >84% annually through year 8, with overall estimates ranging from 81.6% to 90.9% across studies with 4-10 years of follow-up.

Age-related heterogeneity: The lower efficacy observed in participants ≥70 years (73.2%) compared to younger age groups (86.7-87.1%) likely reflects both the increased herpes zoster risk with advancing age and potentially reduced immune responses in the oldest participants. However, the 73.2% efficacy in this oldest cohort still represents substantial clinical benefit.

Consistency across populations: The similar antibody response patterns in general populations, Asian populations, and immunocompromised renal transplant recipients suggests that the fundamental mechanism of RZV-induced immunity is robust across diverse host contexts.

Integration of humoral and cellular immunity: The dual persistence of both antibody responses and cell-mediated responses through 10-11 years suggests that RZV induces coordinated and durable immune memory. The preponderance of evidence indicates that RZV induces sustained immunologic protection lasting at least 10-11 years post-vaccination, with antibody levels plateauing at 5-7-fold above baseline, cell-mediated responses maintained at similar elevations, and vaccine efficacy consistently exceeding 80% in most age groups.