Low concentrations of anti-Abeta antibodies generated in Tg2576 mice by DNA epitope vaccine fused with 3C3d molecular adjuvant do not affect AD pathology

To avoid problems associated with active immunization (e.g., AN-1792) of elderly AD patients, the authors have developed an active vaccination strategy using peptide- or DNA-based epitope vaccines. Here, the authors tested the efficacy of the DNA epitope vaccine p3Abeta 1–11-PADRE and the same vaccine fused with a component of complement 3C3d (p3Abeta 1–11-PADRE-3C3d) in a transgenic (Tg) mouse model of AD (Tg2576), of the H2bxs immune haplotype. The overall responses to both vaccines were very weak in Tg2576 mice despite the fact that the 3C3d molecular adjuvant significantly enhanced the anti-Abeta response to 3Abeta 1–11-PADRE. Importantly, generation of low antibody responses was associated with the strain of amyloid precursor protein Tg mice rather than with a molecular adjuvant, as a p3Abeta 1–11-PADRE-3C3d vaccine induced significantly higher antibody production in another AD mouse model- 3xTg-AD of the H2b haplotype. This study demonstrated that low concentrations of antibodies generated by both DNA vaccines were not sufficient for the reduction of Abeta pathology in the brains of vaccinated Tg2576 animals, confirming previous reports from preclinical studies and the AN-1792 clinical trials. These studies concluded that the concentration of anti-Abeta antibodies may be essential for the reduction of AD pathology.