Efficacy, Immunogenicity and Safety of an Investigational Subunit Adjuvanted Herpes Zoster Vaccine in Adults Aged 60 Years and Older: Results From the ZOE-50 and ZOE-70 Efficacy Studies
Bibliographic record
Abstract
Background. The recombinant herpes zoster (HZ) subunit vaccine candidate (HZ/su) had >90% efficacy (VE) against HZ in older adults in two phase 3 clinical trials (ZOE-50, ZOE-70 [NCT01165177, NCT01165229]). Here we report HZ/su VE against HZ and postherpetic neuralgia (PHN), immunogenicity and safety data in adults ≥60 years of age (YOA) from these studies (VE ≥60 YOA [ZOE-50], immunogenicity/safety 69–69 YOA [ZOE-50], immunogenicity/safety ≥70 YOA [pooled ZOE-50/70]). Methods. Subjects were randomized 1:1 to receive 2 intramuscular doses of HZ/su vaccine (containing 50 µg varicella-zoster virus glycoprotein E [gE] and AS01B Adjuvant System) or placebo (saline solution) 2 months (M) apart. We report VE in reducing HZ and PHN compared to placebo, humoral immune responses (assessed by anti-gE ELISA prior to vaccination and 1, 12, 24 and 36 M post-dose 2 [subset of subjects]) and safety (solicited [diary card subset of subjects] and unsolicited adverse events [AEs] collected for 7 and 30 days after each dose, respectively; medically attended AEs [MAEs] for 6 M after dose 2; fatal events, serious AEs [SAEs] related to vaccination/study participation and potential immune-mediated diseases [pIMDs] until study end [all subjects]). Results. A total of 4490 subjects 60–69 YOA (HZ/su: 2244; control: 2246), 8122 ≥60 YOA (4053; 4069) (ZOE-50) and 17531 ≥70 YOA (8758; 8773) (pooled ZOE-50/70) were vaccinated. VE against HZ in ZOE-50 was 97.6% (95% confidence interval: 92.7–99.6) in adults ≥60 YOA. VE in 60–69 YOA was 97.4% (ZOE-50) and in ≥70 YOA, 91.3% (pooled ZOE-50/70). VE against PHN was 100.0% (55.2–100.0) in adults ≥60 YOA (ZOE-50) and 88.8% in ≥70 YOA (pooled ZOE-50/70) (Table 1). Highest vaccine response rates and geometric mean concentrations of anti-gE antibodies in the HZ/su group were observed 1M post-dose 2. Immune responses persisted for 36M post-vaccination (Figure 1). HZ/su vaccine was more reactogenic than placebo, but reactions were mostly mild or moderate and transient (Figure 2). SAEs, fatal cases and pIMDs were equally distributed between HZ/su group and placebo. Conclusion. In adults ≥60 YOA, HZ/su vaccine is efficacious against HZ and PHN, highly immunogenic and has a clinically acceptable safety profile. Funding. GlaxoSmithKline Biologicals SA. Disclosures. J. E. McElhaney, GSK group of companies: Scientific Advisor and Site PI for clinical trial, Institution received payments for enrollment in clinical trial and Speaker honorarium; H. Lal, GSK group of companies: Employee and Shareholder, Salary and stock; A. L. Cunningham, GSK group of companies: Board Member, My Institution received honorarium for an international advisory board meeting; M. J. Levin, GSK group of companies: Investigator and Scientific Advisor, Consulting fee and Grant recipient. Merck, Sharp & Dohme: Intellectual Property and Scientific Advisor, Consulting fee and patent royalty; R. Chlibek, GSK group of companies: Investigator, Research support; J. Diez-Domingo, SPMSD: Grant Investigator, Scientific Advisor and Speaker's Bureau, Consulting fee, Research grant and Speaker honorarium; H. J. Downey, GSK group of companies, Pfizer, Protein Science: Investigator, Grant recipient; O. Godeaux, GSK group of companies: Former Employee, Salary; I. Gorfinkel, GSK group of companies: Research Contractor, Research grant and Research support; T. Korhonen, University of Tampere, Finland: Employee and Investigator, Salary; S. McNeil, GSK group of companies: Grant Investigator, Collaborative Research Agreement, Grant recipient, Research grant and Research support. Pfizer: Grant Investigator, Collaborative Research Agreement, Grant recipient, Research grant and Research support; K. Pauksens, Akademiska sjukhuset, Uppsala University Hospital: Investigator, The institution received compensation to perform clinical trial; T. J. Avelino-Silva, GSK group of companies: Investigator, Research support; T. Vesikari, University of Tampere: Investigator and Scientific Advisor, Research support; A. Volpi, SanofiPasteur MSD Italy: Scientific Advisor, Salary; D. Watanabe, GSK group of companies: Consultant, Consulting fee; W. Yeo, University of Wollongong: Employee and Investigator, Research support and Salary; L. Campora, GSK group of companies: Employee, Salary; C. Vanden Abeele, GSK group of companies: Employee, Salary; L. Oostvogels, GSK group of companies: Employee, Salary; T. C. Heineman, GSK group of companies: Employee and Shareholder, Salary
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".