Cucumber mosaic virus as the expression system for a potential vaccine against Alzheimer's disease

Abstract

A primary therapeutic goal in Alzheimer's disease (AD) is to reduce the quantity of amyloid β protein (Aβ) present in the brain. To develop an effective, safe system for vaccination against Alzheimer's disease, the plant virus Cucumber mosaic virus (CMV) was engineered genetically to express Aβ-derived fragments that stimulate mainly humoral immune responses. Six chimeric constructs, bearing the Aβ1-15 or the Aβ4-15 sequence in positions 248, 392 or 529 of the CMV coat protein (CP) gene, were created. Viral products proved to be able to replicate in their natural host. However, only chimeric Aβ1-15-CMVs were detected by Aβ1-42 antiserum in Western blot analysis. Experimental evidence of Immunoelectron microscopy revealed a complete decoration of Aβ1-15-CMV(248) and Aβ1-15-CMV(392) following incubation with either anti-Aβ1-15 or anti-Aβ1-42 polyclonal antibodies. These two chimeric CMVs appear to be endowed with features making them possible candidates for vaccination against Alzheimer's disease.