Plant-based vaccines for Alzheimer's disease: an overview.

Plants are considered advantageous platforms for biomanufacturing recombinant vaccines. This constitutes a field of intensive research and some plant-derived vaccines are expected to be marketed in the near future. In particular, plant-based production of immunogens targeting molecules with implications on the pathology of Alzheimer's has been explored over the last decade. These efforts involve targeting amyloid beta and ß-secretase with several immunogen configurations that have been evaluated in test animals. The results of these developments are analyzed in this review. Perspectives on the topic are identified, such as exploring additional antigen configurations and adjuvants in order to improve immunization schemes, characterizing in detail the elicited immune responses, and immunological considerations in the achievement of therapeutic humoral responses via mucosal immunization. Safety concerns related to these therapies will also be discussed.

'Clinical trials in Alzheimer's disease': immunotherapy approaches.

Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid ß (Aß) peptide represents an important molecular target for intervention in Alzheimer's disease. Several types of Aß peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic intact Aß(42) , active immunization involving the administration of synthetic fragments of Aß peptide conjugated to a carrier protein and passive administration with monoclonal antibodies directed against Aß peptide. Pre-clinical studies showed that immunization against Aß peptide can provide protection and reversal of the pathology of Alzheimer's disease in animal models. Indeed, several adverse events have been described like meningoencephalitis with AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several Aß peptide immunotherapy approaches are under investigation but also against tau pathology.

Amyloid beta peptides with an additional cysteine residue can enhance immunogenicity and reduce the amyloid beta burden in an Alzheimer's disease mouse model.

For the development of a safe vaccine for Alzheimer's disease (AD), we studied the immunogenicity of amyloid beta (Abeta) peptides without adjuvant. Addition of a cysteine residue (Cys) to Abeta peptides enhanced immunogenicity in mice compared to those without Cys. Vaccination with the Abeta-Cys peptides reduced Abeta deposits in AD model mice. From these results, the Abeta-Cys peptides, administered without adjuvant, are considered candidates for vaccine therapy for AD.

Refining an Alzheimer's vaccine to avoid an inflammatory response.

The utility of vaccine strategies to treat neurodegenerative diseases such as Alzheimer's disease may still hold promise. Phase IIa clinical trials were halted due to a small but significant occurrence of meningoencephalitis. Knowledge gained from studies on amyloid-beta peptide (Abeta) immunotherapy will allow optimisation of new-generation vaccines, targeting highly specific epitopes while reducing undesired side effects. In harnessing and steering the immune system, an effective response can be generated against Abeta, one that might have attenuated immune responses with robust disease-altering activity.