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Recent reports have demonstrated the ability of anti-prion antibodies to inhibit PrPSc propagation. Due to the relatively poor immunogenic properties of both PrPC and PrPSc, the generation of anti-prion antibodies still causes a significant problem in the development of immunotherapeutic strategies. This study examines the potential of multiple antigenic peptides (MAPs) to raise an antibody response to prion derived sequences in mice. The MAP was constructed of a four spiked ring. Two spikes containing human or mouse derived prion amino acid sequences and two spikes containing the universally promiscuous tetanus toxoid sequence (aa 830–844) which was used to assist T-cell-dependent B-cell antibody production. Following vaccinations with the MAP or MAP plus adjuvant, sera were taken and antibody titres assessed. The MAP containing only the mouse sequence failed to elicit a significant antibody response. MAPs containing human prion sequences elicited antibody production to the corresponding prion sequence. Further analysis also demonstrated that these peptides were able to generate antibody responses that recognize conserved human and mouse sequences. These homologous sequences contain the heralded PrPSc specific sequence ‘Tyr-Tyr-Arg’ and therefore these MAPs may have some therapeutic potential.