An enveloped virus-like particle alum-adjuvanted cytomegalovirus vaccine is safe and immunogenic: A first-in-humans Canadian Immunization Research Network (CIRN) study
Bibliographic record
Abstract
INTRODUCTION: Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). METHODS: Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. RESULTS: Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. CONCLUSIONS: An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".