Species-specific immune response to immunization with human versus rodent A peptide

Amyloid beta (A) immunization of amyloid precursor protein (APP)-transgenic (tg) mice with human A induces humoral immunity, however, the immune response to endogenous rodent A is unknown. Fourteen-month J20 APP-tg mice and non-tg littermates were immunized subcutaneously followed by chronic intranasal boosting with human or rodent A peptide and adjuvant LT(R192G). Rodent A-immunized APP-tg mice had anti-rodent A antibody levels of 257.8g/ml and those immunized with human A had anti-human A antibodies of 120.8g/ml. Non-tg littermates had anti-rodent and anti-human A antibody concentrations of 98.8 and 231.1g/ml, respectively. Inter-species cross-reactivity was minimal. Anti-human A antibodies were predominately IgG1 and IgG2b, while anti-rodent A antibodies were equally IgG1, IgG2a, and IgG2b. Anti-human A antibodies recognized an epitope within human A1–9. Anti-rodent A antibodies did not stain Alzheimer’s disease (AD) plaques but bound some plaques in APP-tg mice. Splenocytes proliferated modestly to their respective antigen and secreted low levels of IL-2 and IFN-. Therefore, immunizing APP-tg and non-tg mice with rodent A resulted in a species-specific humoral response with modest T cell reactivity