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
Notice bibliographique
Résumé
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
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».