Antibody response and plasma Aβ1-40 levels in young Microcebus murinus primates immunized with Aβ1-42 and its derivatives

In the primates, all the peptides administered with alum adjuvant elicited a moderate to robust anti-Aβ IgM response. Aβ1-42, K6Aβ1-30 and K6Aβ1-30[E18E19] resulted in a high anti-Aβ IgG response, whereas Aβ1-30[E18E19] produced a weaker more variable IgG titer. Notably, 22 weeks after the 3rd immunization, IgM and IgG levels in derivative-vaccinated primates were similar to preimmune values whereas Aβ1-42 treated primates maintained a moderate IgG titer. The increase in antibodies that recognized Aβ1-40 often correlated with increase in Aβ1-40 in plasma, which suggests that the antibodies were binding to Aβ in vivo. Interestingly, significant transient weight gain was observed (K6Aβ1-30-, Aβ1-30[E18E19]- and Aβ1-42-treated) or a trend in the same direction (K6Aβ1-30[E18E19]-treated, adjuvant controls) following the injections. Based on these findings, we have chosen K6Aβ1-30 for immunizations in old primates as the antibody response to this vaccine was less variable compared to other Aβ derivatives. Our present findings indicate that most of our Aβ derivatives elicit a substantial antibody response in primates, and importantly this effect is reversible which enhances the safety profile of our approach.