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
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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 source (direct Gemma or distilled Codex), 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".