Preclinical Safety Assessment of the HB-ATV-8 Intranasal Vaccine Designed to Control Atherosclerosis and Metabolic-Associated Fatty Liver Disease.

BACKGROUND AND AIM: The intranasal vaccine HB-ATV-8 contains the Seq-1 peptide (CHLLVDFLQSLS) as the active component within a nanoparticle formulation. It targets the cholesterol ester transfer protein (CETP) by inducing the formation of specific autoantibodies and a cellular antifibrotic response. It has demonstrated efficacy in preventing atherogenesis, liver steatosis, and fibrosis in preclinical models. Given that previously synthesized CETP inhibitors have been associated with increased cardiovascular risk, a preclinical safety assessment of HB-ATV-8 was conducted.

RESULTS

Histopathological analysis of cardiac tissue from control and high-fat diet-fed rabbits treated with HB-ATV-8 revealed no inflammatory damage attributable to the vaccine. To further assess cardiac safety, an in vitro model using cells transfected with the human ether-à-go-go-related gene (hERG) potassium channel was employed to evaluate proarrhythmic potential through cardiac repolarization assessment. Patch-clamp electrophysiology confirmed that the HB-ATV-8 vaccine had no adverse effects on hERG channel kinetics. Genotoxicity was evaluated using the Ames test, which detects point mutations caused by base pair substitutions, additions, or deletions in DNA. The test was performed across multiple Salmonella typhimurium strains. The assays confirmed that HB-ATV-8 is not mutagenic. In addition, positron emission tomography (PET) imaging was performed in dwarf rabbits to evaluate glucose metabolism and systemic effects during vaccine treatment. PET imaging demonstrated that the HB-ATV-8 vaccine does not induce metabolic alterations and provided insights into its biodistribution.

CONCLUSION

Our data fully justify advancing the HB-ATV-8 vaccine into clinical development, where its potential to address both atherosclerosis and metabolic dysfunction-associated fatty liver disease (MAFLD) will be evaluated in human studies.