Safety and Immunogenicity of a Vaccine Against Coxsackieviruses B (PRV-101)—Follow-up of the First-in-Human Phase 1 Trial

Abstract

Background: Coxsackie B viruses cause acute infections and have been linked to chronic diseases like cardiomyopathies, type 1 diabetes, and celiac disease. Despite their clinical significance, no vaccines exist for coxsackie B virus types. PRV-101, a new candidate vaccine covering 5 coxsackie B virus types, showed good immunogenicity and tolerability in a phase 1 trial (PROVENT) in adults. Methods: We conducted an extended follow-up of the PROVENT trial to assess the long-term immune response and safety of PRV-101. A total of 26 participants from the original cohort (n = 32) were enrolled for additional testing ∼2 years postimmunization (11 high-dose, 10 low-dose, and 5 placebo). Coxsackie B virus–specific antibody responses were measured and compared with earlier time points. Results: PRV-101 was safe, with no late adverse effects or emergence of autoantibodies linked to type 1 diabetes or celiac disease. Neutralizing virus antibodies remained elevated, with a clear dose-dependent response. In the high-dose group, antibodies against all coxsackie B virus types reached presumably protective levels, except for coxsackie B virus 2, where 2 participants turned seronegative. Enzyme-linked immunosorbent assay tests confirmed elevated antibody levels against coxsackie B virus proteins. Conclusions: These results suggest that PRV-101 induces durable antibody responses lasting for at least 2 years. The findings support the continued development of PRV-101 for preventing both acute coxsackie B virus infections and chronic diseases like type 1 diabetes and celiac disease.