# 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.

### Records from Elicit search

- n = 200
- Papers screened using: Shingrix Vaccine, Relevant Outcomes, Follow-up Duration, Study Design, Study Population, Quantitative Data, Shingrix Focus, Human Studies

- n = 200 Papers screened out
- n = 190 Papers included for extraction

### Paper search

We performed a semantic search across over 138 million academic papers from the Elicit search engine, which includes all of [Semantic Scholar](https://www.semanticscholar.org/) and [OpenAlex](https://openalex.org/).

We ran this query: “Shingrix glycoprotein E antigen antibody response duration of protection” The search returned 200 total results from Elicit. We retrieved 200 papers most relevant to the query for screening.

### 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)
  - Whether this was an extension study or primary study period
  - Any interim analysis time points reported

- **Anti-gE Antibody Levels**:
  - Measurement method (ELISA, etc.)
  - Antibody concentration values at each time point
  - Units of measurement
  - Geometric mean concentrations (GMCs) or other summary statistics
  - Fold-increase compared to pre-vaccination levels
  - Any thresholds or cut-offs used to define protective levels

- **Vaccine Efficacy**:
  - Overall vaccine efficacy percentages with 95% confidence intervals
  - Annual vaccine efficacy estimates by year post-vaccination
  - Efficacy by age groups if stratified
  - Time period over which efficacy was calculated
  - Any decline or stability patterns in efficacy over time

- **Antibody Persistence**:
  - Description of antibody level changes over time (decline, plateau, stability)
  - Comparison to pre-vaccination baseline levels at latest time points
  - Whether antibody levels remained above specific thresholds
  - Any description of waning or maintenance of immune response
  - Time to return to baseline levels (if applicable)

- **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
  - Geographic location or population characteristics that might affect generalizability of duration data

## 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.

| Study                      | Full text retrieved? | Study type                                 | Maximum follow-up | Sample size          | Population                       | Geographic scope                |
|----------------------------|----------------------|--------------------------------------------|-------------------|----------------------|----------------------------------|---------------------------------|
| C. Boutry et al., 2020     | Yes                  | Extension study (ZOSTER-049, Y2 interim) | 7.1 years         | 7,277 (VE analysis)  | Adults ≥50 years                | International                   |
| C. Boutry et al., 2021     | Yes                  | Extension study (ZOSTER-049)              | 11 years (partial Y8 data) | 7,277 (VE); 813 (humoral) | Mean age 67.2 years           | 18 countries/regions            |
| R. Chlibek et al., 2016    | No                   | Extension study                            | 6 years           | 129                  | Adults ≥60 years                | Czech Republic, Germany, Sweden, Netherlands |
| A. Strezova et al., 2022   | No                   | Extension study (ZOSTER-049, Y4 interim) | 10 years          | 7,277 (VE analysis)  | Adults ≥50 years                | Not specified                    |
| A. Bastidas et al., 2019   | No                   | Extension study                            | 10 years          | 70                   | Adults ≥60 years                | Not specified                    |
| Himal Lal et al., 2015     | Yes                  | Primary study (ZOE-50)                    | 3.2 years (mean) | 15,411               | Adults ≥50 years; mean age 62.3 years | 18 countries across Europe, North America, Latin America, Asia-Australia |
| Ana Strezova et al., 2025   | Yes                  | Extension study (ZOE-LTFU, final analysis)| 11 years          | 7,273                | Mean age 67.3 years at first vaccination | 18 countries/regions            |
| J. Kim et al., 2021        | Yes                  | Sub-analysis of ZOE-50/70                 | 4 years (median)  | 2,729 (≥50 years); 2,723 (≥70 years) | Asian adults; mean age 62.0-76.0 years | Hong Kong, Japan, South Korea, Taiwan |
| P. Vink et al., 2019       | Yes                  | Primary study                              | 12 months         | 264                  | Renal transplant recipients; mean age 52.3-52.4 years | 9 countries (Belgium, Canada, Czech Republic, Finland, Italy, Panama, Republic of Korea, Spain, Taiwan) |
| OUP accepted manuscript      | No                   | Primary study                              | 5 years           | 160                  | Adults aged 50-85 years        | Not specified                    |

Most studies were extension trials following participants from the pivotal ZOE-50 and ZOE-70 trials, with the longest follow-up reaching 11 years post-vaccination. Three studies specifically examined the ZOSTER-049 extension cohort at different interim time points. Sample sizes ranged from 70 participants in smaller extension cohorts to over 15,000 in the primary ZOE-50 trial. The majority of participants were of European ancestry (76%), though one study specifically examined Asian populations and another focused on immunocompromised renal transplant recipients.

### 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. Antibody levels were reported in milli-international units per milliliter (mIU/mL).

| Study                      | Pre-vaccination GMC | Peak GMC (timing)                          | Latest time point GMC | Fold-increase at latest time point | Pattern                          |
|----------------------------|----------------------|--------------------------------------------|-----------------------|--------------------------------------|----------------------------------|
| C. Boutry et al., 2020     | Not specified         | Not specified                              | Not specified (Y8)    | 6-fold above baseline                  | Stable and high                  |
| C. Boutry et al., 2021     | 1320.5 mIU/mL        | 17,296.9 mIU/mL (Y1)                     | 8053.5 mIU/mL (Y5)    | >6-fold                              | Plateaued at ~6-fold            |
| R. Chlibek et al., 2016    | 1121.3 mIU/mL        | Not specified                              | 8159.0 mIU/mL (72 months)  | 7.3-fold                            | Decreased 20-25% from month 36 but remained elevated |
| A. Strezova et al., 2022   | Not specified         | Not specified                              | Not specified (Y10)   | >5-fold                              | Maintained                       |
| A. Bastidas et al., 2019   | Not specified         | Plateaued around Y3                       | Not specified (Y10)    | 5.9-fold                            | Plateaued from Y3 to Y10        |
| Ana Strezova et al., 2025   | Not specified         | Not specified                              | 6844.3 mIU/mL (Y12)   | 5-5.8-fold (Y5-Y12)                | Plateaued at >5-fold; stable Y5-Y8, modest decrease Y9, stable through Y12 |
| P. Vink et al., 2019       | 1354.4 mIU/mL        | 19,163.8 mIU/mL (1M post-dose 2)         | 8545.1 mIU/mL (12M post-dose 2) | 6.3-fold (12M post-dose 2) | Increased then persisted above baseline |

Anti-gE antibody concentrations demonstrated a consistent pattern across studies. Following an initial peak at approximately one month post-second dose (range 17,296.9-19,163.8 mIU/mL), antibody levels declined but plateaued at sustained elevations above baseline. The plateau phase typically began around year 3 post-vaccination and persisted through the longest follow-up periods. At 6 years post-vaccination, antibodies remained 7.3-fold above pre-vaccination levels (8159.0 vs. 1121.3 mIU/mL). The longest follow-up data showed antibody concentrations sustained at 5- to 7-fold above baseline through 10-12 years.

A modest decline in geometric mean concentrations (GMCs) was observed in the 6-year follow-up study, where antibody levels decreased by 20-25% between months 36 and 72, yet remained substantially elevated compared to pre-vaccination (8159.0 vs. 1121.3 mIU/mL at month 72). The 11-year follow-up showed stable GMCs from year 5 to year 8, a modest decrease at year 9, and then stabilization through year 12 at 6844.3 mIU/mL. Despite these fluctuations, antibody levels never returned to baseline during any study period.

In the immunocompromised renal transplant population, antibody responses followed a similar pattern with peak GMCs of 19,163.8 mIU/mL at one month post-dose 2, declining to 8545.1 mIU/mL by 12 months post-dose 2 but remaining 6.3-fold above baseline.

### 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.

| Study                      | Overall VE (95% CI)                         | Follow-up period   | Annual VE pattern              | Age-stratified VE                |
|----------------------------|---------------------------------------------|----------------------|---------------------------------|----------------------------------|
| C. Boutry et al., 2020     | 84.0% (75.9-89.8%) during ZOSTER-049; <br> 90.9% (88.2-93.2%) from 1M post-dose 2 | Y2 interim (5.1-7.1 years mean) | Stable and high                | Not specified                    |
| C. Boutry et al., 2021     | 84.0% (75.9-89.8%) from ZOSTER-049 start; <br> 90.9% (88.2-93.2%) from vaccination | 5.1-7.1 years mean  | >84% each year; plateaued >84% Y4-Y6 | Not stratified                    |
| A. Strezova et al., 2022   | 81.6% (75.2-86.6%) during ZOSTER-049; <br> 89.0% (85.6-91.3%) from 1M post-dose 2 | 10 years            | High and stable                  | Not specified                    |
| A. Bastidas et al., 2019   | ≥90%                                       | Not specified        | Not specified                    | Not specified                    |
| Himal Lal et al., 2015     | 97.2% (93.7-99.0)                       | 3.2 years mean      | Not specified                    | 96.6-97.9% across age groups     |
| Ana Strezova et al., 2025   | 79.8% (73.7-84.6%) for ≥50 years; <br> 73.2% (62.9-80.9%) for ≥70 years <br> 87.7% (84.9-90.1%) from 1M post-dose 2 | 11 years           | Y6-8: 83.9-82.8%; Y9: 73.7%; Y10: 71.7%; Y11: 82.0% | 50-59 years: 86.7%; <br> 60-69 years: 87.1%; <br> ≥70 years: 73.2% |
| J. Kim et al., 2021        | 95.6% (86.4-99.1) for ≥50 years; <br> 94.7% (85.9-98.6) for ≥70 years | 4 years median      | >90% all age strata; no significant change over 4 years | >90% across age strata           |

The primary ZOE-50 trial demonstrated exceptionally high initial vaccine efficacy of 97.2% (95% CI: 93.7-99.0) over a mean follow-up of 3.2 years, with efficacy ranging from 96.6% to 97.9% across age groups (50-59, 60-69, ≥70 years). This high level of protection was maintained in the Asian sub-analysis, which showed 95.6% efficacy in adults ≥50 years and 94.7% in adults ≥70 years over 4 years, with no significant decline during the follow-up period.

Extended follow-up through the ZOSTER-049 study showed vaccine efficacy remained above 84% annually from years 4 through 6, and overall efficacy of 84.0% (95% CI: 75.9-89.8%) during at least 2 years of follow-up in the interim analysis. When calculated from 1 month post-dose 2 through the year 2 interim analysis, overall efficacy was 90.9% (95% CI: 88.2-93.2%). The 10-year interim analysis reported vaccine efficacy of 81.6% (95% CI: 75.2-86.6%) during the ZOSTER-049 study period and 89.0% (95% CI: 85.6-91.3%) from 1 month post-dose 2 through year 10.

The final 11-year analysis revealed more detailed temporal patterns. Annual vaccine efficacy remained stable between 83.9% and 82.8% during years 6-8, decreased to 73.7% during year 9 and 71.7% during year 10, but rebounded to 82.0% during year 11. Overall vaccine efficacy during the ZOE-LTFU study was 79.8% (95% CI: 73.7-84.6%) for participants ≥50 years and 73.2% (95% CI: 62.9-80.9%) for participants ≥70 years. When calculated from 1 month post-dose 2 through the end of the 11-year follow-up, overall efficacy was 87.7% (95% CI: 84.9-90.1%). Age-stratified analysis at 11 years showed efficacy of 86.7% in the 50-59 year age group, 87.1% in the 60-69 year age group, and 73.2% in the ≥70 year age group.

### 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. By 6 years post-vaccination, the gE-specific cell-mediated immune response was 3.8 times higher than pre-vaccination values (477.3 vs. 119.4 activated gE-specific CD4+ T cells per 10^6 cells). This cellular response plateaued at approximately 3.3-fold above pre-vaccination levels starting around year 4 and persisting through year 10. The 11-year follow-up showed that cell-mediated immune responses plateaued at approximately 7-fold above pre-vaccination levels.

In the comparative study examining RZV versus live zoster vaccine, RZV recipients demonstrated significantly higher gE-specific responses measured by interferon-γ (IFN-γ) and interleukin 2 (IL-2) at all time points post-immunization. Only RZV recipients maintained higher post-vaccination gE-specific IL-2+ and IFN-γ+ responses for 5 years, suggesting that the 5-year persistence of VZV-specific memory and gE-specific Th1 immunity may underlie superior RZV efficacy.

### 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. No safety concerns arose, and overall occurrences of renal function changes, rejections, serious adverse events, and potential immune-mediated diseases were similar between RZV and placebo groups.

## 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. The 20-25% decline observed between months 36 and 72 in one study and the modest decrease at year 9 in another appear to represent normal antibody homeostasis rather than immunologic waning, as levels remained substantially above the 97 mIU/mL seropositivity cutoff and stabilized rather than continuing to decline.

**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. The decrease to 73.7% during year 9 and 71.7% during year 10, followed by a rebound to 82.0% during year 11, likely reflects statistical variation in small numbers of breakthrough cases in the aging cohort rather than a true immunologic decline. This interpretation is supported by the maintained antibody plateau during this same period and the subsequent rebound in efficacy.

**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, particularly given that these participants were 72.5 years old on average at the start of the long-term follow-up study and reached ages in the early 80s by the end of follow-up. The initial ZOE-50 trial showed similar high efficacy (96.6-97.9%) across all age groups, suggesting that aging during the follow-up period may contribute to the observed differences.

**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. The 6.3-fold sustained elevation at 12 months in renal transplant recipients is comparable to the 5-7-fold plateau observed in immunocompetent populations at later time points.

**Integration of humoral and cellular immunity**: The dual persistence of both antibody responses (5-7-fold above baseline) and cell-mediated responses (3.3-7-fold above baseline) through 10-11 years suggests that RZV induces coordinated and durable immune memory. The finding that only RZV (not live zoster vaccine) maintained gE-specific memory responses through 5 years provides mechanistic support for the superior long-term efficacy observed in clinical trials.

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. While minor fluctuations occur, particularly in years 9-10, the overall trajectory demonstrates stability rather than progressive waning.

## References

[R. Chlibek, K. Pauksens, L. Rombo, Gini G C van Rijckevorsel, J. Richardus, and 5 more (2016). Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults. Vaccine](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-18552843/index.html)

[A. Strezova, J. Díez-Domingo, Kamal Al Shawafi, J. Tinoco, Meng Shi, and 2 more (2022). 114. Long-term Protection Against Herpes Zoster (HZ) by the Adjuvanted Recombinant Zoster Vaccine (RZV): Interim Efficacy, Immuno and Safety Results at Approximately 10 Years after Initial Vaccination. Open Forum Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-254756786/index.html)

[A. Bastidas, Grégory Catteau, S. Volpe, T. Mrkvan, Adaora Enemuo, and 8 more (2019). 2905. Long-term Immunological Persistence of the Adjuvanted Recombinant Zoster Vaccine: Clinical Data and Mathematical Modeling. Open Forum Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-204946418/index.html)

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[C. Boutry, Andrew Hastie, Meng-yuan Shi, J. Díez-Domingo, J. Tinoco, and 4 more (2020). 8. The Adjuvanted Recombinant Zoster Vaccine (RZV) Confers Long-term Protection Against Herpes Zoster: Interim Results of an Extension Study (ZOSTER-049) of Two Clinical Trials (ZOE-50 and ZOE-70). Open Forum Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-230800008/index.html)

[Ana Strezova, Javier Díez Domingo, A. Cunningham, Takashi Eto, C. Andrews, and 16 more (2025). Final analysis of the ZOE-LTFU trial to 11 years post-vaccination: efficacy of the adjuvanted recombinant zoster vaccine against herpes zoster and related complications. EClinicalMedicine](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-278478858/index.html)

[C. Boutry, Andrew Hastie, J. Díez-Domingo, J. Tinoco, Chong-Jen Yu, and 164 more (2021). The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70. Clinical Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-236140427/index.html)

[J. Kim, John Diaz-Decaro, Ning Jiang, Shinn-Jang Hwang, E. Choo, and 15 more (2021). The adjuvanted recombinant zoster vaccine is efficacious and safe in Asian adults ≥ 50 years of age: a sub-cohort analysis of the ZOE-50 and ZOE-70 randomized trials. Human Vaccines & Immunotherapeutics](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-231969052/index.html)

[P. Vink, J. M. Ramón Torrell, A. S. Sánchez Fructuoso, Sung-Joo Kim, Sang-Il Kim, and 23 more (2019). Immunogenicity and Safety of the Adjuvanted Recombinant Zoster Vaccine in Chronically Immunosuppressed Adults Following Renal Transplant: A Phase 3, Randomized Clinical Trial. Clinical Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-73474039/index.html)

[No authors found (2021). OUP accepted manuscript. Journal of Infectious Diseases](/content/review/5af48c25-392b-4f4c-83ab-3e29c77101d2/source/ss-244683236/index.html)