Optimized vaccine candidate generates enhanced polyclonal antibody response against pyroglutamate Abeta in non-human primates
Phase 2 interim analysis of ACI-24 confirms good safety and tolerability profile in people with mild Alzheimer’s disease
Pyroglutamate Abeta (pyroGlu-Abeta) is a highly neurotoxic form of Abeta that is N-terminally truncated and post-translationally modified to form pyroglutamate. Extracellular pyroGlu-Abeta is an important target for immunotherapy, as the peptide’s altered biochemical properties make it more prone to aggregate compared to full-length Abeta, and it is a major component of Abeta plaques. Passive immunization with a monoclonal antibody specific for pyroglutamate Abeta demonstrated encouraging clinical results in a recently published Phase 2 clinical study.
In non-human primates, vaccination with the optimized ACI-24 vaccine generated a strong, conformation-specific antibody response against oligomeric and pyroGlu-Abeta. A robust boosting effect was also observed, the magnitude of which was substantially greater against pyroGlu-Abeta compared to full-length Abeta (approx. 8-fold vs 4-fold increase, respectively, between the 3rd and 5th injections). Epitope mapping studies using sera from immunized cynomolgus monkeys showed the strongest signals for sites binding to peptides covering N-terminal regions of Abeta located just beyond where cleavage occurs to form pyroGlu-Abeta (amino acids 3-10, 4-11, 5-12). This further supports the strong response observed against this key pathological variant.
About the SupraAntigen® platform
AC Immune’s clinically validated SupraAntigen® platform uses proprietary liposomes to rapidly generate novel vaccines (SupraAntigen®-V) for active immunization as well as best-in-class monoclonal antibodies (SupraAntigen®-A) for passive immunization against key neurodegenerative disease targets. Antibodies generated by the platform are highly specific for the pathological conformations of misfolded proteins and show good safety in AD patients and animals. The SupraAntigen® platform has successfully generated two vaccines and two monoclonal antibody candidates that have been validated in clinical studies and has led to multiple global partnerships with world-leading pharmaceutical companies. In addition to targeting Abeta and Tau,
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