The present disclosure is directed to alpha-synuclein (αSyn) peptide immunogen constructs, compositions containing the constructs, antibodies elicited by the constructs, and methods for making and using the constructs and compositions thereof. The disclosed αSyn peptide immunogen constructs contain a B cell epitope from αSyn linked to a heterologous T helper cell (Th) epitope directly or through an optional heterologous spacer. The B cell epitope portion of the peptide immunogen constructs contain about (10) to about (25) amino acid residues of αSyn, corresponding to the sequence from about the Glycine at position 111 (G111) to about the Asparagine at position (135) (D135) of full-length αSyn. The α-Syn peptide immunogen constructs stimulate the generation of highly specific antibodies that are cross-reactive with the beta-sheet of αSyn as monomers, oligomers, and fibrils, but not the natural alpha-helix of αSyn, offering therapeutic immune responses to hosts at risk for synucleinopathies.
