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Design and Characterization of Peptide Amphiphile-Based Immunotherapeutics: Amyloid- Peptides and Alzheimer's Disease

Amanda Trent, Dimitris Missirils, and Matthew Tirrell. University of California, Santa Barbara, Materials Research Laboratory, MC5121, University of California, Santa Barbara, CA 93106-5121

Peptides play a critical role in determining the magnitude and specificity of

cellular and humoral immunity. For this reason, peptide-based antigens capable of

stimulating a specific and efficient immune response have long been sought to treat or

prevent infectious diseases and other chronic ailments such as cancer. However,

strategies for developing peptide-based immunotherapy face significant hurdles,

including achieving potent immunogenicity, minimizing toxicity, and overcoming

delivery challenges.

One possible alternative for satisfying these requirements is the design of peptide

amphiphiles (PA), in which peptide antigens acylated with hydrophobic carbon tails can

self-assemble into supra-molecular aggregates. The general properties of PA aggregates,

including the multivalent presentation of antigen, the flexibility to control formation of

various micellar and vesicular structures for delivery purposes, and the fact that peptide

secondary structure is induced upon assembly, make PAs attractive for

immunotherapeutic drug design. Moreover, the potential of hydrophobic tails to act as

adjuvants may render the use of common toxic adjuvants dispensable.

We propose using amyloid-β peptides (involved in Alzheimer's Disease

pathology) as model antigens to demonstrate the proof-of-principle concept of PA-based

vaccines. Data revealing aggregate size, shape, composition, and peptide conformation

will be presented. Subsequent to this basic physical characterization, in vitro assays as

well as animal studies will be used to determine the strength and specificity of the

elicited immune response of the amyloid-β constructs.