Journal of the American Medical Directors Association
Review ArticleActive Vaccines for Alzheimer Disease Treatment
Section snippets
Methods
PubMed and Scopus were searched using keywords “Alzheimer Vaccine” and “Alzheimer Active Vaccine.” Clinical trial articles describing next generation and first generation active Alzheimer disease vaccine were selected as well as relevant recent review articles and relevant preclinical studies to the field of active Alzheimer disease vaccines were selected. Because many active Alzheimer disease vaccines are still in clinical trials, ClinicalTrials.gov was searched for “Alzheimer Vaccine,”
Active Alzheimer Disease Vaccines
This review describes the first generation active Aβ42 vaccine AN1792 clinical trials, the next generation of Aβ and tau active vaccines currently in clinical trials, and future directions. A summary of the Alzheimer disease active vaccine clinical trials is provided in Table 1.
CAD106
CAD106 targets antibody production against the Aβ 1-6 amino acid peptide fragment to serve as a B-cell epitope while avoiding a T-cell response.16 The peptide is coupled with a carrier with 180 copies of the bacteriophage Qβ protein coat to aid in induction of an immune response.16 In a phase 1 trial in patients with mild-to-moderate Alzheimer disease, no clinical or subclinical cases of meningoencephalitis were recorded.16 Sixteen of 24 patients (67%) who received CAD106 50 μg and 18 of 22
Discussion
Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. In the first generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease, 6% of patients (18 of 298) treated with the vaccine (AN1792) developed meningoencephalitis, whereas none of the 74 patients in the control group did.13 Nineteen antibody generating patients who received a prime and boost of AN1792 remained unchanged
Conclusions
The first generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis.13 Because of this, next generation vaccines are working to target more specific epitopes to induce a more controlled immune response.16 Though much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea
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R.M.S. is supported by the Mayo Clinic Medical Scientist Training Program Robert L. Howell Physician-Scientist Scholarship.
The authors declare no conflicts of interest.