JNHA - The Journal of Nutrition, Health and Aging

, Volume 13, Issue 3, pp 264–267

Development of AFFITOPE vaccines for Alzheimer’s disease (AD) — From concept to clinical testing

  • A. Schneeberger
  • M. Mandler
  • O. Otava
  • W. Zauner
  • F. Mattner
  • W. Schmidt
Second Generation AD Vaccines

DOI: 10.1007/s12603-009-0070-5

Cite this article as:
Schneeberger, A., Mandler, M., Otava, O. et al. J Nutr Health Aging (2009) 13: 264. doi:10.1007/s12603-009-0070-5

Abstract

Based on the notion that cerebral accumulation of certain Aβ species is central to AD pathogenesis and endowed with the knowledge that emerged during clinical testing of the first human Alzheimer vaccine, AN1792, we designed a new generation of Alzheimer vaccines. Rather than relying on full-length Aβ itself or fragments thereof, AFFITOPE vaccines use short peptides, mimicking parts of the native Aβ sequence, as their antigenic component. The technology created to identify these peptides, termed AFFITOPE-technology, at the same time provides the basis for the multi-component safety concept realized in AFFITOPE vaccines. First, as they are non-self, AFFITOPES don’t need to break tolerance typically established against self proteins. This allows us to use aluminium hydroxide, the agent first approved as immunological adjuvant for human use and, thus, exhibiting an excellent safety profile. Second, AFFITOPES employed in Alzheimer vaccines are only 6 amino acids in length, which precludes the activation of Aβ-specific autoreactive T cells. Third, and above all, the AFFITOPE technology allows for controlling the specificity of the vaccine-induced antibody response focusing it exclusively on Aβ and preventing crossreactivity with APP. In a program based on two AFFITOPES allowing neoepitope targeting of Aβ (free N-terminus), this approach was taken all the way from concept to clinical application. Early clinical data support the safety concept inherent to AFFITOPE Alzheimer vaccines. Further clinical testing will focus on the identification of the optimal vaccine dose and immunization schedule. Together, result of these trials will provide a solid basis for clinical POC studies.

Key words

Alzheimervaccineimmunotherapydisease modificationclinical study

Abbreviations

Aa

amino acid

amyloid β

Ab

antibody

AD

Alzheimer’s disease

AD

adverse event

APP

Amyloid Precursor Protein

BBB

blood brain barrier

CMI

cell mediated immunity

FDA

Federal Drug Agency

IFN

Interferon

ME

meningoencephalitis

NINCDS/ADRDA

National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria

POC

Proof of concept

SUSAR

suspected unexpected serious adverse reaction

Copyright information

© Serdi and Springer Verlag France 2009

Authors and Affiliations

  • A. Schneeberger
    • 1
  • M. Mandler
    • 1
  • O. Otava
    • 1
  • W. Zauner
    • 1
  • F. Mattner
    • 1
  • W. Schmidt
    • 1
  1. 1.AFFiRiSViennaAustria