Prokaryote-derived phosphorylated Tau epitope vaccine is immunogenic and non-T-cell activated in the mice model.

Accumulation of phosphorylated Tau protein is a prominent pathological hallmark of Alzheimer's disease (AD). However, current vaccines targeting phosphorylation sites are primarily modified using chemical reactions, which exhibit low efficiency in terms of linking to the vaccine carrier. Despite the identification of over 2000 phosphorylation sites on approximately 20% of E. coli proteins through proteomic studies, it remains unclear whether recombinant Tau proteins expressed in bacteria undergo direct phosphorylation. Additionally, limited information is available regarding the immunogenicity and safety profiles of prokaryotic-derived pTau epitope vaccines. Our study discovered that the prokaryotic system can induce phosphorylation on four residues (T181, T205, S262, and S396) of the full-length Tau protein. Based on this finding, we developed a prokaryotic-modified phosphorylated Tau protein vaccine and immunized wild-type mice, resulting in enhanced immunogenicity and a favorable safety profile.