Protocol · graded by use, two uses
Shingles vaccination (recombinant zoster vaccine), for shingles and dementia
Shingles (herpes zoster) in adults aged 50 and older.
At a glance
This is about the shingles shot, given twice a few months apart. In two large studies of adults 50 and older, it prevented about 9 in 10 cases of shingles compared with a dummy shot. Side effects are common. Most people get a sore arm or feel unwell for a day or two. About 1 in 6 felt bad enough to miss normal activities. A rare nerve illness, Guillain-Barré syndrome, was a few cases per million shots more common in the 6 weeks after. Some studies found less dementia after an older shingles shot, but no fair test has checked this yet. Two have started.
- What was measured
- Shingles confirmed by a lab test of the rash, counted for about 3 to 4 years after two shots, in adults 50 and older.
- How big
- Confirmed shingles fell from 9.1 to 0.3 cases per 1,000 people each year, over 3.2 years on average. The trial in older adults found a similar drop.Read from the summary of PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 25916341.
- Who it applies to
- Adults 50 and older without a weakened immune system, given the newer two-dose shot. It does not cover the older live shot, and dementia has not yet been tested in a trial.
- Safety
- Sore arms and feeling unwell for a day or two are common, and about 1 in 6 felt bad enough to miss normal activities. A rare nerve illness, Guillain-Barré syndrome, was a few cases per million shots more common in the 6 weeks after.
- Compared with
- Two dummy shots of salt water.
- Certainty
- Grade A, resting on: Randomized placebo-controlled trials for shingles; natural experiments and observational Research that watches what people already do rather than assigning a treatment. It can show that two things travel together, not that one causes the other. studies, no randomized trial yet, for dementia.
- What would change this grade
- Could move down to B if this trial found no benefit: Large randomized trial run independently of the vaccine maker, comparing the recombinant vaccine with placebo An inactive substitute made to look like the real treatment, so participants cannot tell which one they received.. Who: Adults aged 50 and older without immune compromise. Measured: Shingles confirmed by PCR testing of the rash. Length: At least 3 years of follow-up.
- Cost
- No price recorded yet.
- Sources
- 11 studies cited on this record, listed under Sources.
The A belongs to one of the two uses graded on this record. The other one carries its own letter.
This record carries a separate letter for each thing it has been measured on. The headline grade is the best of them, and it does not transfer to the others.
ZOE-50 (Lal et al., N Engl J Med, 2015; PMID 25916341): 15,411 adults aged 50 and older; laboratory-confirmed shingles in 6 vaccine and 210 placebo recipients, efficacy 97.2%, similar in every age group. ZOE-70 (Cunningham et al., N Engl J Med, 2016; PMID 27626517): 13,900 adults aged 70 and older; 23 against 223 cases, efficacy 89.8%, and 89.1% at 80 and older. A disease event confirmed in the laboratory, replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away. in two large trials: A. Both trials were funded and run by GlaxoSmithKline, the maker; under the replication rule same-maker trials count, and the funding is stated here.
No randomized trial has measured dementia. The evidence is natural experiments of the live vaccine, which compare people born just either side of a date that decided eligibility: in Wales, new dementia diagnoses were 3.5 percentage points fewer over 7 years among those vaccinated (Eyting et al., Nature, 2025; PMID 40175543); in Australia, eligibility lowered them 1.8 percentage points over 7.4 years (Pomirchy et al., JAMA, 2025; PMID 40267506); in Ontario, 2.0 percentage points over 5.5 years (Pomirchy et al., Lancet Neurol, 2026; PMID 41579903); and in Wales, mild cognitive impairment diagnoses and deaths from dementia were also fewer (Xie et al., Cell, 2025; PMID 41338191). For the recombinant vaccine the evidence is observational: a comparison of recombinant against live vaccine recipients (Taquet et al., Nat Med, 2024; PMID 39053634) and a Medicare target trial emulation, funded by the maker, whose negative-control analyses suggested some residual confounding (Hayes et al., Ann Intern Med, 2026; PMID 42296498). Under Rule 05 a letter rests only on randomized trials, so this use is D, not yet tested, until a trial reports.
Funding: Both randomized trials replicating this Grade A for Shingles (herpes zoster) in adults aged 50 and older were funded by the maker of the product they tested, GlaxoSmithKline Biologicals. The funder's role in design and analysis is not stated here, because the full trial reports could not be read. The letter stands because each trial met the grading rules on its own; the funding is stated here so it can be weighed alongside it. Investigators: Both randomized trials replicating this Grade A for Shingles (herpes zoster) in adults aged 50 and older were run by investigators employed by, founded by, or belonging to the organization that developed, sells or teaches the intervention (GlaxoSmithKline, the vaccine maker, whose employees are among the authors). The funder may read non-commercial; the people who ran the trials are part of the organization whose intervention they tested, which is stated here so it can be weighed alongside the letter.
The recombinant shingles vaccine is two injections given 2 to 6 months apart. In two large placebo-controlled trials in adults aged 50 and older it prevented about 9 in 10 cases of shingles. Separately, natural experiments in Wales, Australia and Canada found fewer dementia diagnoses among people who became eligible for the older live shingles vaccine, but no randomized trial has yet measured dementia, so that use carries no letter above D. Two randomized trials with dementia as an outcome are under way. Graded by use.
Why this letter
Why this gradeThe reasoning, and what the grade does not cover.
Grade A on shingles in adults aged 50 and older: two large observer-blind placebo-controlled trials found confirmed shingles about 90% less frequent, in adults aged 50 and older (ZOE-50; Lal et al., 2015; PMID 25916341) and in adults aged 70 and older (ZOE-70; Cunningham et al., 2016; PMID 27626517). A disease event confirmed in the laboratory, replicated in two trials, so A; both were funded and run by the maker, as the funding line beside the letter states. Grade D on dementia, Route 1 No human randomized trial has been run, so the record rests on animal or mechanistic evidence only. One of the two routes to the lowest letter on EBL's scale., not yet tested: no randomized trial has reported dementia as an outcome. The natural experiments in Wales, Australia and Canada (PMIDs 40175543, 40267506, 41579903) compare people born just either side of an eligibility date and are the strongest observational evidence of their kind, but they studied the live vaccine, they are not randomized trials, and under Rule 05 a letter rests only on randomized trials. Two randomized trials with dementia as an outcome are under way (NCT07502560, NCT07485283).
WHAT THIS GRADE DOES NOT COVERthe live shingles vaccine, which is no longer sold in the United States and was not tested in these trials; adults under 50 or people with weakened immune systems, who were excluded from the graded trials; and memory or thinking in people who already have dementia.
Shared endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score.: Laboratory-confirmed shingles against saline placebo, adults aged 50 and older without weakened immune systems
- ZOE-50, multicenter, 18 countries (Lal): Shingles 0.3 against 9.1 per 1,000 person-years, efficacy 97.2%, 15,411 adults aged 50 and older, mean 3.2 years. PMID 25916341 · Funding: manufacturer-funded (GlaxoSmithKline Biologicals)
- ZOE-70, multicenter, 18 countries (Cunningham): Shingles 0.9 against 9.2 per 1,000 person-years, efficacy 89.8%, 13,900 adults aged 70 and older, mean 3.7 years. PMID 27626517 · Funding: manufacturer-funded (GlaxoSmithKline Biologicals)
What the replication does not cover: Different age groups and separate randomizations, run in parallel at the same centers by the same sponsor. Neither enrolled people with weakened immune systems.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
Who responds: this record's trial reading reports no subgroup that identifies who responds.
ClinicalTrials.gov, the public registry run by the U.S. National Library of Medicine, lists studies that are recruiting volunteers. The link below searches it for Recombinant Zoster Vaccine among studies recruiting now. EBL has no relationship with any listed study and receives no payment for this link.
Search recruiting studies of Recombinant Zoster Vaccine on ClinicalTrials.gov
Evidence notes: randomized trial, independently replicated, industry-sponsored
Endpoint graded: Confirmed shingles (herpes zoster) in adults aged 50 and older (hard)
Last reviewed: October 2026
Dose, form and timing
Measured outcome in the graded trials: shingles confirmed by laboratory testing of the rash (PCR), counted over 3 to 4 years after two doses. In the dementia studies: a new dementia diagnosis in health records, or dementia recorded as a cause of death.
As studiedDose, form, population and duration for every use.
A grade describes the intervention that was tested. Where the product on the shelf differs from it, this says so.
Safety
Side effects are common. In the efficacy trials, 79.0% of vaccinated adults aged 70 and older had injection-site or whole-body reactions within 7 days, against 29.5% on placebo (ZOE-70; PMID 27626517), and 17.0% had a reaction severe enough to prevent normal activity, against 3.2% (ZOE-50; PMID 25916341); serious adverse events, immune-mediated diseases and deaths were similar in both groups. After licensing, two Medicare analyses found a higher risk of Guillain-Barré syndrome, a nerve disorder that causes weakness, in the 42 days after vaccination: about 3 extra cases per million doses (Goud et al., JAMA Intern Med, 2021; PMID 34724025) and 6.6 per million, after the first dose, in 3.4 million adults aged 65 and older (Dos Reis et al., Drug Saf, 2026; PMID 41910703). VAERS, the US Vaccine Adverse Event Reporting System, received 66,849 reports after this vaccine from October 2017 to April 2024, 97.3% classed non-serious, most often injection-site reactions, fever, chills, headache and fatigue, and including 86 reports of death (Shu et al., Prev Med Rep, 2025; PMID 39901936). Anyone can file a VAERS report, reports are not verified, and the system does not know how many people were vaccinated, so a report does not show that the vaccine caused the event and the counts are not rates. Its role is to raise signals, as it did for Guillain-Barré syndrome, which the Medicare studies then measured. The reports can be searched at the system's public site, vaers.hhs.gov.
Cautions documented in human studies. Each caution on this record, sorted by what it rests on.
- Reactions: 79.0% of vaccinated adults 70 and older had injection-site or whole-body reactions against 29.5% on placebo, 17.0% severe against 3.2% (PMID 27626517 PMID 25916341)
- Guillain-Barre syndrome: Medicare analyses found about 3 to 6.6 extra cases per million doses in the 42 days after vaccination (PMID 34724025 PMID 41910703)
- VAERS: 66,849 reports from 2017 to 2024, 97.3% non-serious, including 86 death reports, unverified reports that are not rates or proof of cause (PMID 39901936)
None recorded.
None recorded.
Does not apply: human harm data are listed above.
Grade history
How this letter has changedLatest: No. 383 · October 2026 · First graded.
The recombinant shingles vaccine now has its own record, graded by use. In two observer-blind placebo-controlled trials, it prevented about 9 in 10 cases of laboratory-confirmed shingles in adults aged 50 and older (Lal et al., 2015; PMID 25916341) and 70 and older (Cunningham et al., 2016; PMID 27626517): A, with the maker's funding of both trials stated beside the letter. Dementia is D, Route 1: natural experiments in Wales, Australia and Canada found fewer dementia diagnoses after the live vaccine (Eyting et al., 2025; PMID 40175543; Pomirchy et al., 2025; PMID 40267506), but no randomized trial has yet reported dementia, and two are under way. Harms are on the record beside the benefit: reactions severe enough to stop normal activity in 17.0% against 3.2% on placebo (PMID 25916341), and about 3 to 7 extra cases of Guillain-Barré syndrome per million doses in Medicare data (Goud et al., JAMA Intern Med, 2021; PMID 34724025; Dos Reis et al., Drug Saf, 2026; PMID 41910703). Applied the written grade definitions under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 25916341 PMID 27626517 PMID 40175543 PMID 40267506 PMID 34724025 PMID 41910703
Every change to a letter on this site is dated and published. The full evidence log →
Sources
- Citations
- Every paper cited on this page is matched to its PubMed record on every build.
- Retractions
- None of these papers is retracted or under a journal expression of concern. PubMed is checked again on every build.
- Read against the papers
- October 2026. By the EBL editor, Arnold Sandlow, DC.
- Outside review
- Not yet done. No reviewer outside EBL has checked this record.
What each of these checks can and cannot show: evidence integrity.
The evidence, in fullEleven papers, each linked to its PubMed record.
ZOE-50 (Lal et al., N Engl J Med, 2015; PMID 25916341): 15,411 adults aged 50 and older in 18 countries, two doses of adjuvanted recombinant glycoprotein E vaccine or saline placebo, observer-blind, mean follow-up 3.2 years; confirmed shingles 6 against 210 cases (0.3 against 9.1 per 1,000 person-years), efficacy 97.2% (95% CI 93.7 to 99.0). ZOE-70 (Cunningham et al., N Engl J Med, 2016; PMID 27626517): 13,900 adults aged 70 and older, mean age 75.6, mean follow-up 3.7 years; 23 against 223 cases, efficacy 89.8% (84.2 to 93.7), similar at 70 to 79 and 80 and over; pooled with ZOE-50 participants aged 70 and older, efficacy against postherpetic neuralgia 88.8%. Both trials were funded and run by GlaxoSmithKline, the maker, with company employees among the authors. Dementia, natural experiments of the live vaccine: Eyting et al. (Nature, 2025; PMID 40175543), Wales, eligibility set by date of birth, vaccination 0.01% against 47.2% either side of the cut-off, new dementia diagnoses 3.5 percentage points fewer over 7 years among the vaccinated (relative 20.0%); Pomirchy et al. (JAMA, 2025; PMID 40267506), Australia, 101,219 patients, eligibility lowered new dementia diagnoses by 1.8 percentage points over 7.4 years; Pomirchy et al. (Lancet Neurol, 2026; PMID 41579903), Ontario, 232,124 patients, 2.0 percentage points fewer over 5.5 years at each of two thresholds; Xie et al. (Cell, 2025; PMID 41338191), Wales, fewer diagnoses of mild cognitive impairment and fewer deaths from dementia among people already living with it. Dementia, recombinant vaccine, observational: Taquet et al. (Nat Med, 2024; PMID 39053634), recombinant against live vaccine recipients, 17% more time free of a dementia diagnosis over 6 years; Hayes et al. (Ann Intern Med, 2026; PMID 42296498), 509,926 Medicare beneficiaries after a skilled-nursing stay, target trial emulation, 4-year dementia risk 18.8% against 24.6%, with negative-control analyses suggesting some residual confounding, funded by GlaxoSmithKline. The natural experiments were funded by the US National Institutes of Health and academic sources, as stated in the papers. Harms: ZOE-50 and ZOE-70 report reactions within 7 days and serious adverse events (PMIDs 25916341, 27626517); Goud et al. (JAMA Intern Med, 2021; PMID 34724025), Medicare self-controlled case series, Guillain-Barré syndrome relative risk The risk in one group expressed as a share of the risk in another. It can make a small absolute difference look large. 2.84 in the 42 days after vaccination, about 3 extra cases per million doses; Dos Reis et al. (Drug Saf, 2026; PMID 41910703), 3,383,799 Medicare beneficiaries, relative risk 3.15, 6.59 extra cases per million doses, after dose 1 and not dose 2; Shu et al. (Prev Med Rep, 2025; PMID 39901936), VAERS reports October 2017 to April 2024, 66,849 after this vaccine, 97.3% non-serious, 86 reporting death.
How EBL searched for the trials (1 search)
The search that was run, what it returned, and what was left out and why, so the absence of evidence can be checked as well as its presence.
(zoster vaccin*[tiab] OR "recombinant zoster"[tiab] OR Shingrix[tiab] OR Zostavax[tiab] OR "herpes zoster subunit"[tiab]) AND randomized controlled trial[pt] AND (efficacy[tiab]) AND (incidence[tiab] OR "herpes zoster"[ti])PubMed watch: does a new study change the grade? (nothing new)
No new paper matching the search behind this grade has been added to PubMed since October 2026.
Last run October 2026. A letter on EBL moves only after a logged review. A new paper never moves a letter by arriving: it is read, the answer is written here, and any change to the letter is published in the evidence log.
Disclosure
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
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