Safety, tolerability and immunogenicity of PRV-101, a multivalent vaccine targeting coxsackie B viruses (CVBs) associated with type 1 diabetes: a double-blind randomised placebo-controlled Phase I trial

• DOI: 10.1007/s00125-024-06092-w
• Publication Date: 2024-02-19T01:01:51Z
• Authors: Heikki Hyöty; Susanna Kääriäinen; Jutta E. Laiho; Gail M. Comer; Wei Tian; Taina Härkönen; Jussi P. Lehtonen; Sami Oikarinen; Leena Puustinen; Michele Snyder; Francisco León; Mika Scheinin; Mikael Knip; Miguel Sanjuan
• Keywords: Tolerability

Abstract Aims/hypothesis Infection with coxsackie B viruses (CVBs) can cause diseases ranging from mild common cold-type symptoms to severe life-threatening conditions. CVB infections are considered be prime candidates for environmental triggers of type 1 diabetes. This, together the significant disease burden acute and their association chronic other than diabetes, has prompted development human vaccines. The current study evaluated safety immunogenicity first vaccine designed against CVBs associated diabetes in a double-blind randomised placebo-controlled Phase I trial. Methods main eligibility criteria participants were good general health, age between 18 45 years, provision written informed consent willingness comply all trial procedures. Treatment allocation (PRV-101 or placebo) was based on computer-generated randomisation schedule people assessing outcomes masked group assignment. In total, 32 (17 men, 15 women) aged 18–44 years receive low ( n =12) high dose multivalent, formalin-inactivated including serotypes 1–5 (PRV-101), placebo =8), given by intramuscular injections at weeks 0, 4 8 single site Finland. followed another 24 weeks. Safety tolerability primary endpoints. Anti-CVB IgG virus-neutralising titres analysed using an ELISA neutralising plaque reduction assays, respectively. Results Among (low dose, =12; placebo, =8) no serious adverse events leading treatment discontinuation observed. Treatment-emergent related drug occurred 37.5% 62.5% PRV-101 (injection pain, headache, injection discomfort pruritus being most common). induced dose-dependent antibody responses five included both high- low-dose groups. Protective ≥8 seen >90% over entire follow-up period. Conclusions/interpretation results indicate that tested multivalent is well tolerated immunogenic, supporting its further clinical development. Trial registration ClinicalTrials.gov NCT04690426. Funding This funded Provention Bio, Sanofi company. Graphical