Review Article
Active Vaccines for Alzheimer Disease Treatment

https://doi.org/10.1016/j.jamda.2016.06.009Get rights and content

Abstract

Introduction

Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression.

Methods

PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed.

Results

First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis.

Conclusions

Although 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 of active vaccination for Alzheimer disease very appealing and something worth striving toward.

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

References (38)

  • S. Todd et al.

    Survival in dementia and predictors of mortality: A review

    Int J Geriatr Psychiatry

    (2013)
  • L. Rizzi et al.

    Global epidemiology of dementia: Alzheimer's and vascular types

    Biomed Res Int

    (2014)
  • W. Kaplan et al.

    Priority Medicines for Europe and the World “A Public Health Approach to Innovation”

  • L.M. Waite

    Treatment for Alzheimer's disease: Has anything changed?

    Aust Prescr

    (2015)
  • M. Allgaier et al.

    An update on drug treatment options of Alzheimer's disease

    Front Biosci (Landmark Ed)

    (2014)
  • R.P. Alves et al.

    Alzheimer's disease: Is a vaccine possible?

    Braz J Med Biol Res

    (2014)
  • J.E. Morley et al.

    A physiological role for amyloid-beta protein: Enhancement of learning and memory

    J Alzheimers Dis

    (2010)
  • J.M. Orgogozo et al.

    Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization

    Neurology

    (2003)
  • B. Vellas et al.

    Long-term follow-up of patients immunized with AN1792: Reduced functional decline in antibody responders

    Curr Alzheimer Res

    (2009)
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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.

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