Attempts to Develop Vaccines Against Alzheimer's Disease: A Systematic Review of Ongoing and Completed Vaccination Trials in Humans.

In this systematic review, we evaluate the safety, tolerability, and immunogenicity of vaccination efforts against Alzheimer's disease (AD) in human subjects from both ongoing and completed vaccination trials. Databases like PubMed, Embase, and Scopus were used to identify relevant articles on completed vaccination trials whereas the clinicaltrials.gov database was used for identifying ongoing clinical trials for vaccination against AD in humans until January 2022. Only interventional randomized or non-randomized clinical trials which reported on the safety and immunogenicity of vaccine against AD in humans were included. Cochrane risk of bias tool-2 (RoB-2) or risk of bias in non-randomized studies- of intervention (ROBINS-I) was used for risk of bias assessment as appropriate. A narrative descriptive synthesis of the findings was done. Sixteen randomized/non-randomized clinical trials (phase I: six and phase II: 10) for seven different types of vaccines against AD were identified comprising a total of 2080 participants. Apart from the development of meningoencephalitis in 6% of patients receiving AN1792 in an interrupted phase II trial, the rest of the trial reported promising results on the safety and immunogenicity of vaccines. While only a subset of reported adverse events was treatment related, none of the fatalities reported during the trial were considered related to vaccine administration. The serological response rate ranged from 100% (4/16 trials) to 19.7% in an interrupted trial. Although current trials show promising results, adequately powered phase III studies are needed to conclusively establish the safety, immunogenicity and therapeutic efficacy of vaccines.