LB18. An Enveloped Virus-like Particle (eVLP) Cytomegalovirus (CMV) Vaccine Is Immunogenic and Safe: Results of a First-in-Humans Study
Bibliographic record
Abstract
Abstract Background CMV is the most common cause of congenital infection and may result in permanent neurodevelopmental injury including vision and hearing loss. A vaccine to prevent transmission of CMV during pregnancy or to immunocompromised persons is a public health priority. Neutralizing antibodies (nAb) to the CMV envelope glycoprotein B (gB) in natural infection are thought to confer protection, but some vaccine candidates based on this protein alone have been insufficiently immunogenic. In this FiH dose-ranging, controlled, observer-blinded study the safety and immunogenicity of an eVLP expressing the ectodomain of gB fused to transmembrane and cytoplasmic domains of the vesicular stomatitis virus G protein (gB-G) was evaluated. Method Healthy CMV-seronegative 18–40 year olds at three sites in Canada (Vancouver, Montreal, Halifax) were randomized to one of four dose formulations (0.5 µg, 1 µg, or 2 µg gB content with Alum) or 1 µg gB without Alum, or placebo given on days 0, 56, and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB binding antibody titers and avidity assessment, and nAb to CMV infection of fibroblast and epithelial cells. A Data Safety Monitoring Board was in place. Result Among 128 participants, the most common solicited local and general AEs were pain and headache, respectively. No SAEs or withdrawals occurred. A dose-dependent boosting of nAb titers was observed after doses 2 and 3, with the highest titers in the Alum-adjuvanted 2.0 µg dose recipients. Fibroblast cell nAb were seen in 100% of 2.0 µg dose recipients, and epithelial cell nAb in 31%. Epithelial cell nAb was correlated with higher geometric mean gB binding titers, and there was a correlation between fibroblast and epithelial cell nAb titers. Conclusion An eVLP CMV vaccine was immunogenic at very low doses in healthy seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and multiple doses. This phase 1 trial supports further development of this eVLP CMV vaccine candidate. ClinicalTrials.gov NCT02826798 Disclosures S. Gantt, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. C. Quach, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. D. E. Anderson, VBI Vaccines: Employee and Shareholder, Salary. F. Diaz-Mitoma, VBI Vaccines: Consultant and Shareholder, Salary. J. Langley, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".