A Randomized First-in-Human Study With UB-312, a UBITh® α-Synuclein Peptide Vaccine.
Level 2 - randomized trial
Randomized, placebo-controlled, double-blind trial
PubMed 35426173 · doi:10.1002/mds.29016
What was done
A 44-week, randomized, placebo-controlled, double-blind first-in-human study evaluated the safety, tolerability, and immunogenicity of UB-312, a synthetic alpha-synuclein peptide vaccine conjugated to a T helper peptide. Fifty healthy participants across seven cohorts were randomized to receive three intramuscular injections of UB-312 (doses from 40 to 2000 μg) or placebo at weeks 1, 5, and 13. Safety was evaluated via adverse events, clinical laboratory tests, vitals, electrocardiograms, and physical/neurological exams. Immunogenicity was measured via anti-alpha-synuclein antibody levels in serum and cerebrospinal fluid (CSF).
What was found
Twenty-three participants received all three active UB-312 vaccinations. Adverse events were mostly mild, transient, and self-resolving, with headache, nasopharyngitis, injection-site pain, lumbar puncture-site pain, and fatigue being most common. UB-312 induced dose- and time-dependent antibody production. Anti-alpha-synuclein antibodies were detectable in both serum and CSF in 100% of participants receiving the 300/300/300 μg regimen, showing an average CSF/serum ratio of 0.2%.
Why it matters
This study provides first-in-human evidence that active immunization against alpha-synuclein is feasible and generates antibodies that penetrate the central nervous system, supporting phase 2 clinical testing in Parkinson's disease.
Limits
The study sample was small (n = 50 total across seven cohorts, with only 23 completing the full active vaccine course) and evaluated only healthy adults, leaving safety and therapeutic efficacy in Parkinson's disease unmeasured. Detailed quantitative antibody titers and exact adverse event incidence rates were not reported in the abstract.
Cited by
- supports Vaxxinity has developed an alpha-synuclein targeting vaccine for Parkinson's disease that has completed Phase 1 and entered Phase 2 clinical trials.