Phospho-Tau Antibody Delivery Using Virus-Like Nanoparticles as Carriers Enhances Spatial Memory Functions in Tauopathy Model Rats

Abstract

Background: Anti-tau immunotherapies targeting phospho-epitopes have shown promising outcome in pre-clinical studies, although, with certain limitations in terms of mode of antibody delivery and concentration of antibodies required to obtain positive outcome. Results & methods:In this study, virus-like particles containing 180 binding sites for antibodies per particle was chosen as the antibody delivery tool. Antibodies against phospho-tau-peptide (sequence 50-71 AA) phosphorylated at S68, T69, and T71 were coated onto chimeric Sesbania mosaic virus-like nanoparticles containing B domain from S. aureus (SLB). SLB bound antibodies showed enhanced binding to tau protein as compared to unconjugated antibodies. Passive immunization studies were conducted in okadaic acid (OKA) induced tauopathy model rats. In Barnes maze task, SLB-Ab treated rats exhibited marked learning ability in comparison to OKA rats, with progressive decrease in the number of errors made and the time taken in reaching the escape hole.Conclusions: These results suggest the merits of SLB-Ab in improving spatial memory as reflected by far lesser number of SLB-Ab injections required to observe the therapeutic effect.