Differences in the immune response to long term Aβ vaccination in C57BL/6 and B6D2F1 mice

The cerebral accumulation of β-amyloid (Aβ) is a pathological hallmark of Alzheimer’s disease (AD). Aβ vaccination or anti-Aβ specific antibodies may be a possible therapeutic option for AD. Previously, we demonstrated variation in the humoral response between B6D2F1 and C57BL/6 during short term (14 weeks) Aβ immunization. In the present study, we determined the humoral and cellular immune responses in these same mouse strains to a longer period of Aβ vaccination and further refined the major B cell epitope to Aß1–7. B6D2F1 mice generated a greater humoral and Th1 immune response versus C57BL/6 mice. Immunization with 25μg Aβ produced a greater T cell response in B6D2F1 mice compared to 50 or 100μg Aβ but resulted in comparable humoral immunity. Thus, Aβ vaccination is affected by the genetic background and amount of Aβ peptide used as immunogen. These data may help explain some differences observed in Aβ immunization studies in mice of various genetic backgrounds and aid in the design of Aβ vaccines.