Vaccine Design And Construction Based On Two Known Epitope Fragments Of Tau

One of the biggest challenges in global health and social care in the 21 st century is dementia.Alzheimer’s disease(AD)is the most common dementia,characterized by its irreversible and progressive loss of function,loss of cognitive and behavioral abilities,usually accompanied by various brain diseases,such as agnosia,ataxia,and aphasia or even death.There are dozens of pathogenic hypotheses about Alzheimer’s disease.The most important hypothesis among them is acetylcholine hypothesis,but it no longer received much attention as time goes by.The extensively studied clinical trials of Aβ drugs or immunopharmaceuticals have frequently ended in failure.Currently,hypothesis of abnormal protein modification of tau received much more attention.The tau hypothesis is mainly about hyperphosphorylation or abnormal truncation of tau protein,which would lead to dissociation from microtubules,the continuously gathering of tau into pairs of spiral filaments in the cell could result in neurofibrillary tangles(NFTs),and eventually cause neuronal cell death.A full-length tau protein whole yeast vaccine had been previously constructed in our lab and was used to immunize BALB/c mice orally.The results of specific antibodies against full-length tau detected by ELISA were fairly good,and specific antibodies were not detected in a stable manner,indicating that the full-length tau protein is prone to misfolding,so that the effective antigenic determinant cannot be recognized,and the immunogenicity is low.In this study,tau 175-305 fragment was selected as the shortened antigen,and BALB/c mice were immunized by injection and gavage,and the mouse serum was collected for ELISA analysis.The results show that the gavage method of administration can produce specific Ig G1 and Ig A antibodies,which have a regular increasing trend over time and the antibody level is stable.The purpose of the oral whole yeast vaccine in this study is to stimulate intestinal mucosal immunity,and the elicited specific antibodies being able to block the transmission of tau between neuronal cells,thereby slowing down the disease progression.Nevertheless,this new therapeutic strategy needs more studies on AD model mice in order to be considered as a candidate immunotherapy for AD.