Dual Aβ/tau epitope vaccines: a poorly explored strategy for Alzheimer's disease immunotherapy

Alzheimer's disease (AD) presents a growing public health challenge that urgently requires effective disease-modifying therapies. Active immunotherapy appears to be a promising strategy in AD drug development, offering advantages over passive immunization in terms of prophylactic potential and cost-effectiveness. We systematically reviewed anti-Aβ and anti-tau active immunization strategies over the past 25 years, identifying 577 unique antigenic formulations. Only 3.5 % have progressed to clinical trials, with none yet approved. Notably, only three strategies targeted both Aβ and tau epitopes (Aβ1-11 and tau2-18), despite the potential of multi-target approaches for AD's multifactorial pathology. Given the synergistic role of Aβ and tau in disease progression, dual-target vaccines remain a critical and underinvestigated area with significant therapeutic promise. This review underscores the need to expand research into multi-target immunotherapies that better address AD's complexity, potentially improving prevention and treatment outcomes.