INTRODUCTION TO AFFITOME® TECHNOLOGY
AFFITOME® technology relies on the use of lookalikes of native antigen molecules. In conventional vaccines, native antigens are used which have an inherent risk of inducing autoimmunity.
AFFITOME® technology allows:
- avoidance of cellular and humoral autoimmunity
- targeting of neo-epitopes, i.e. disease-specific structures
This is accomplished by using AFFITOPEs®, short peptides mimicking parts of the native sequence or structure of the neo-epitope. AFFITOPEs® are identified with a “selecting antibody.” It is the features of this selecting antibody that will be translated to the humoral immune response elicited by the given AFFITOPE®.
To this end, the pool of all possible peptides of a predefined length is screened for those binding to the selecting antibody. The binding ones will have imprinted the specific features of the selecting antibody. Upon immunization with these AFFITOPE® candidates, the imprinted features are passed onto the resulting antibodies. Candidates only become true AFFITOPEs® if they are immunogenic, transfer the features of the selecting antibody, and are successful in proof of concept studies.
Using AFFITOME® technology in SYMPATH
AFFiRiS identified within a preclinical screening program a series of α-Syn vaccine candidates. Two, PD01A and PD03A, were selected for early clinical development based on a set of features including the specificity of the immune response they induce, and promising results of proof of concept studies in various animal models and their favorable safety profile obtained by standard toxicity testing. PD01A and PD03A represent, developmentally, the most advanced members of the α-Syn-targeting vaccine family.
While both fulfill all of the above criteria, they differ in their physicochemical properties (amino acid sequence, length), immunologic fine specificity and performance in various model systems. PD01A entered clinical testing early 2012 as the first α-Syn-targeting immunotherapeutic drug ever tested in humans representing a new class of drugs.
In SYMPATH, the consortium takes a powerful and straightforward effort to advance early clinical development of PD01A and PD03A in two indications, Parkinson´s disease and multiple system atrophy, each with an urgent need for a causal therapy.
For additional information on the AFFITOME® technology, please see:
- Schneeberger et al. AFFITOME® Technology in neurodegenerative diseases. The doubling advantage. Human Vaccines 6:11 948-952. 2010.
- Schneeberger et al. Development of AFFITOPE vaccines for Alzheimer´s disease. From concept to clinical testing. J Nutr Health Aging. 13:264-7. 2009.
- Mandler et al. Next‑generation active immunization approach for synucleinopathies: implications for Parkinson’s disease clinical trials. Acta Neuropathol DOI 10.1007/s00401-014-1256-4. 2014.