The present invention is generally directed to HER-2/neu fusion proteins, nucleic acid molecules encoding HER-2/neu fusion proteins, viral vectors expressing HER-2/neu fusion proteins, and pharmaceutical compositions (e.g., vaccines) comprising the HER-2/neu fusion proteins and/or nucleic acid molecules encoding the HER-2/neu fusion proteins. The present invention is also directed to methods of treating or preventing cancer by eliciting or enhancing an immune response to the HER-2/neu protein, including for uses in the treatment of malignancies associated with the HER-2/neu oncogene.