A Virus-Like-Particle-Based Conjugate Vaccine Targeting the Microtubule Binding Region of Tau Protein

There is a pressing need to develop novel strategies to ameliorate symptoms and slow the progression of Alzheimer's disease. One of the hallmarks of Alzheimer's disease is the high levels of tau protein, which can form toxic oligomers and characteristic neurofibrillary tangles in the brain. Antitau antibodies can potentially bind tau protein and reduce tau pathology. In order to elicit a powerful antitau antibody response, virus-like-particle bacteriophage Qβ-based conjugate vaccines were developed targeting the microtubule binding region of tau protein. The Qβ-tau vaccines were able to produce a strong antitau antibody response in not only wild-type mice but also in human tau transgenic mice and a llama. The levels of antibody induced were superior to those generated by a corresponding keyhole limpet hemocyanin-based tau conjugate mimicking the one vaccine that successfully completed phase 1/2 human clinical trials. The Qβ-tau vaccine significantly improved the cognitive functions of the immunized mice and reduced the levels of inflammatory cytokines and tau in the brains, suggesting its translational potential.