Therapeutic Potential of Vaccines for Alzheimer‘s Disease

Abstract

The pathological hallmarks of Alzheimer‘s disease (AD) are amyloid-β (Aβ) plaques and Tau-containing neurofibrillary tangles. Although the relationship between neuronal loss and the presence of plaques/tangles is not well understood, the prevailing Aβ hypothesis posits that excessive accumulation of conformers and assemblies of Aβ protein precedes AD-related dementia and neuronal loss. Consequently, most disease-modifying immunotherapy approaches are directed towards modulating the levels of Aβ. The first AD vaccine clinical trial (AN1792) was suspended after the patients developed meningoencephalitis. In spite of the setback, the trial provided insights to refine development second-generation vaccines, which are attempting to resolve the side effects observed in the trial. This article provides an analysis of these efforts.

KEYWORDS::

• active immunization
• DNA vaccine
• HSV-1
• immunotherapy
• peptide vaccine
• rAAV
• single-chain antibody

Financial & competing interests disclosure

Howard J Federoff has filed patents on the use of HSV amplicons for gene transfer and immunization. He is a founder of MedGenesis Ltd and a equity owner in this company. Howard J Federoff has previously received grants from the NIH to fund work on HSV amplicons. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Howard J Federoff has filed patents on the use of HSV amplicons for gene transfer and immunization. He is a founder of MedGenesis Ltd and a equity owner in this company. Howard J Federoff has previously received grants from the NIH to fund work on HSV amplicons. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.