We have been developing Aβ derivative vaccines with the objective to improve the safety of Aβ targeting immunotherapy. Our Aβ homologs are designed to have less direct toxicity and to produce a modified immune response compared to Aβ. In extensive mouse studies, all our vaccines have improved cognition in transgenic mice while eliciting different immune responses and reducing brain amyloid burden to a variable degree. While we are continuing to characterize these vaccines in mice, in preparation for studies in old primates and for human trials we assessed their effect in young lemur primates (n=25) that with age develop Aβ plaques and tau aggregates as seen in Alzheimer's disease. 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.