A Phase I Randomized, Observer-Blind, Controlled, Dose Escalation Trial of the Safety and Tolerability of Two Intramuscular Doses of DPX-RSV(A), a Respiratory Syncytial Virus (RSV) Vaccine Containing RSV SH Antigen and a Novel Adjuvant DepoVax, or SH Antigen Co-administered With Aluminum Hydroxide, or Placebo to Healthy Adults ≥50–64 Years of Age
Notice bibliographique
Résumé
Background. RSV causes lower respiratory tract infection in children, the immunosuppressed, and older adults. Currently, there is no licensed vaccine for RSV infection. Subsequent to pre-clinical studies showing proof of principle, we are conducting a first-in-humans study of a novel RSV antigen (Ag) from the ectodomain of the Short Hydrophobic protein of RSV, formulated in the lipid and oil-based vaccine platform, DepoVax, termed DPX-RSV(A) (NCT02472548). Methods. Healthy persons 50 to 64 years of age in good general health were enrolled beginning May 2015, and randomized 2:2:1 in to two dose levels of a DPX-RSV(A) (10 or 25 µg), or synthetic RSV SH Ag with or without 125 µg Aluminum hydroxide, or saline placebo control. Dose escalation occurred in two sequential steps. A booster dose was given at Day (D) 56. Per protocol, if any participant in any vaccine group had anti-SH antibody (Ab) on D28, then the RSV(A)-Alum groups received a placebo booster. Participants and observers were blinded to allocation. Solicited local and general adverse events (AE) were collected on a memory aide D0-6 post-injection and unsolicited AE through to D28 post-injection. Serious AE (SAE), medically attended AE (MAE), and potentially immune mediated disease (pIMD) were collected to D236. Blood samples for IgG Ab to SH Ag and hematologic or biochemical parameters were collected on D 0, 7, 28, 56, 63, 84 and 236; immunogenicity results are in progress. The study is ongoing. Results. With 40 participants enrolled, the mean age was 55.3 years (SD 3.97); 72.5% were female. Ab response was detected at D28, so RSV(A)-Alum subjects received placebo for dose 2 (D56). Pain was the most common local AE, reported in 14/40 (37.5%) overall; 14/15 had Grade (Gr) 1 pain and 1 had Gr 2 pain. No swelling or redness occurred D0-6. Pain did not increase with dose 2. Drowsiness (0-37.5% per group; all Gr 1) and muscle aches (0-25% per group; 7 subjects rated grade 1 and 1 rated Gr 3) were most common solicited general AE. Unsolicited AE occurred in 25-75% of subjects per group. MAEs occurred in all groups except RSV(A)-Alum 10 µg (total n = 8). No pIMD or SAE occurred. Antigen-specific immune responses to RSV SH were demonstrated post vaccination. Conclusion. A novel RSV Ag from the SH protein of RSV, formulated in the lipid and oil-based vaccine platform, DepoVax, had an acceptable safety and induced antigen specific antibody responses. Disclosures. J. Langley, Immunovaccine: Grant Investigator, Research support. GlaxoSmithKline: Investigator, Research grant. Novavax: Investigator, Research grant; L. MacDonald, Immunovaccine Inc.: Employee, Salary; G. Weir, Immunoivaccine: Employee, Salary; S. McNeil, GSK: Grant Investigator, Research grant and Research support; B. Schepens, VBI: Employee, Salary; X. Saelens, VIB: Employee and VIB and UGhent hold patent rights on SHe-based vaccines and treatment options for RSV: patent application WO2012/065997 (24.05.2012) with Bert Schepens, Walter Fiers, and Xavier Saelens as inventors, Salary; M. Stanford, Immunovaccine Inc.: Employee, 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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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) | 0,000 | 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 tête enseignante, 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 ».