The present invention concerns methods for selecting and producing idiotype vaccines, and in particular methods for selecting and producing an idiotype vaccine for treatment of a B-cell derived malignancy in a subject based on the clonal profile (clonotype) of the malignancy; a method for producing an updated idiotype vaccine matched to a B-cell derived malignancy exhibiting a shifting clonal profile; and the high-fidelity idiotype vaccines produced using the methods. The invention also includes idiotype vaccines produced using the described methods and methods of treating B-cell derived malignancies using the produced vaccines.