UB-312 synuclein vaccine

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Vaxxinity (US). Part A paper by Yu, Thijssen, van Brummelen and colleagues; the Parkinson's paper by Eijsvogel, Misra and colleagues (corresponding author Jean-Cosme Dodart), run at the Centre for Human Drug Research in the Netherlands. A small NYU Langone study (Horacio Kaufmann) tested it in Parkinson's and MSA.

What happened

UB-312 is an active vaccine: a short piece of alpha-synuclein attached to a helper sequence so the body makes its own antibodies. It follows earlier vaccine attempts (landmark 103).

• Part A (Movement Disorders 2022;37:1416–1424, DOI 10.1002/mds.29016). 50 healthy volunteers; 23 got all three injections (weeks 1, 5, 13). Doses ranged from 40 to 2,000 micrograms. The adverse events matched placebo. Antibodies reached spinal fluid at about 0.2% of the blood level.
• Part B (Parkinson's, NCT04075318; Nature Medicine 2024;30:2631–2640, DOI 10.1038/s41591-024-03101-8). 20 people, recruited Oct 2021 to Apr 2022: 6 placebo, 7 on 300/100/100 µg, 7 on 300/300/300 µg, followed 44 weeks. Of 13 who completed dosing, 12 made antibodies in blood (5 of 6 and 7 of 7) and antibodies were found in spinal fluid in 5 (4 of 6 on the lower regimen, 1 of 7 on the higher one), peaking at week 21 and fading by week 45. The seed amplification assay (landmark 9) dropped 19.8% on the lower-dose regimen (p<0.05) and 15.2% on the higher (not significant). Motor and thinking scores were stable, with no difference between groups; a gain in daily-living scores (MDS-UPDRS Part II) in the five people with detectable spinal-fluid antibodies was a post hoc finding the authors call anecdotal. Three serious adverse events occurred in two people, including one deep vein thrombosis judged possibly related to the vaccine. Vaxxinity's June 2023 release said 92% of the 13 developed antibodies, which matches 12 of 13.
• NCT05634876 (NYU, Phase 1b). 8 people with Parkinson's or MSA (four of each, per Alzforum), 300 µg, three priming and five booster injections (Alzforum); started 31 May 2023, finished 11 February 2025. Primary measures are antibody levels in blood and spinal fluid. No results posted.

Why it moved us toward a cure

It showed a vaccine can be given safely and may nudge the seeding signal down. It also showed the weakness: the antibody that reaches the brain is tiny and short-lived. The later ACI-7104 programme in landmark 103 is the live version of the idea.

It follows the first synuclein vaccine tested in people, PD01A (landmark 324).

Outcome

Open but quiet. Proof of concept for immune response only. No Phase 2 is registered on ClinicalTrials.gov, and Alzforum (updated July 2024) describes no Phase 2 plans.

Sources

• NeurologyLive on the Parkinson's results, 9 Jul 2024 · NeurologyLive on Part A/B
• Yu et al., Mov Disord 2022, DOI 10.1002/mds.29016 · Eijsvogel et al., Nat Med 2024, DOI 10.1038/s41591-024-03101-8, PMC11405261 · NCT04075318 (70 enrolled, results posted)
• ClinicalTrials.gov NCT05634876 · Vaxxinity release, June 2023 (BioSpace)
• Not yet verified: the NYU study's results; whether Vaxxinity has plans or funds for Phase 2.