{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:34:45Z","timestamp":1787726085776,"version":"build-2784847793"},"reference-count":10,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Parkinson\u2019s disease (PD) is a major neurodegenerative disorder with no cure. The goal is to develop an active immunotherapy targeting aggregated alpha synuclein (aSyn), the root cause of PD. TRB-001 is the lead candidate of a novel class of vaccines. It is a peptide\/protein conjugate coupled to sugar residues, which is used to target and activate antigen-presenting cells, and addresses aSyn. Methods: A 33-year-old male, diagnosed with PD seven years previously, with a Hoehn &amp; Yahr stage of 1, taking Levodopa\/Benserazide (100\/25 mg, 6\u00d7 per day), Rotigotine (8 mg) and Rasagiline (1 mg), amounting to a Levodopa equivalent daily dose (LEDD) of 940 mg, also complicated by impulse control disorder, requested experimental therapy. He received a total of four TRB-001 administrations (weeks 0, 4, 8 and 34) following informed consent. The workup included safety, immunological and clinical parameters. Results: Vaccinations were well tolerated. They induced a high-titer aSyn-specific antibody (Ab) response. Titer increase was associated with a reduction in aSyn plasma levels, suggesting target engagement. The Ab titer and the reduction in aSyn plasma levels were both long-lived. The boost elicited a recall-type Ab titer increase and triggered avidity maturation (factor 7.8). Abs demonstrated a high degree of selectivity for aggregated aSyn (factor 30). Moreover, they were found to preferentially react with tissue from PD brain lysates. The Movement Disorder Society-Sponsored Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) score for the patient remained essentially stable throughout the observation period of 53 weeks. At the time of the boost, the symptomatic PD therapy was simplified to Levodopa\/Carbidopa\/Entacapone 100\/25\/200 mg four times a day, amounting to an LEDD of 532 mg. This put an end to the symptoms of the impulse control disorder. Conclusions: Results obtained suggest that this new class of vaccines may yield Ab responses comparable in magnitude and target avidity to the therapeutic setting of monoclonal Abs. TRB-001 is currently being translated to a randomized, placebo-controlled Phase 1B study.<\/jats:p>","DOI":"10.3390\/vaccines14060466","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:45:08Z","timestamp":1779673508000},"page":"466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Case Report of a Novel Alpha-Synuclein Vaccine (TRB-001) in a Parkinson\u2019s Patient: Safe Administration and Induction of a High-Titer, High-Avidity Functional Antibody Response"],"prefix":"10.3390","volume":"14","author":[{"given":"Dieter","family":"Volc","sequence":"first","affiliation":[{"name":"Atomos Clinic Waehring, 1180 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Thun-Hohenstein","sequence":"additional","affiliation":[{"name":"Atomos Clinic Waehring, 1180 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Schmidhuber","sequence":"additional","affiliation":[{"name":"Tridem Bioscience, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Mandler","sequence":"additional","affiliation":[{"name":"Tridem Bioscience, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9410-124X","authenticated-orcid":false,"given":"Achim","family":"Schneeberger","sequence":"additional","affiliation":[{"name":"Tridem Bioscience, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0140-6736(23)01429-0","article-title":"Medical, Surgical, and Physical Treatments for Parkinson\u2019s Disease","volume":"403","author":"Foltynie","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"578047","DOI":"10.1016\/j.jneuroim.2023.578047","article-title":"A functional role of Alpha-synuclein in Neuroimmune responses","volume":"376","author":"Heiden","year":"2023","journal-title":"J. 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