Efficacy and Safety of the Immunization with DNA for Alzheimer’s Disease in Animal Models: A Systematic Review from Literature

Abstract

Background:Alzheimer’s disease (AD) is a neurodegenerative disease that does not have a proven cure; however, one of the most promising strategies for its treatment has been DNA vaccines.Objective:The present review is aimed to report the new developments of the efficacy and safety of DNA vaccines for AD in animal models.Method:The method PRISMA was used for this review. The article search was made in the electronic databases PubMed, LILACS, and Scopus using the descriptors ‘’Alzheimer disease” and ‘’Vaccine, DNA”. Articles published between January 2001 and September 2017 in English, Portuguese, and Spanish were included.Results:Upon the consensus, the researchers identified 28 original articles. The studies showed satisfying results as for the decrease of amyloid plaques in mouse, rabbits, and monkeys brains using mostly the DNA Aβ42 vaccine, AV-1955, and AdPEDI-(Aβ1-6)11, mainly with a gene gun. In addition to a reduction in tau by the first DNA vaccine (AV-1980D) targeting this protein. The use of adjuvants and boosters also had positive results as they increased the destruction of the amyloid plaques and induced an anti-inflammatory response profile without side effects.Conclusion:The results of DNA vaccines targeting the amyloid-β and the tau protein with or without adjuvants and boosters were promising in reducing amyloid plaques and tau protein without side effects in animals. Although there are many vaccines being tested in animals, few reach clinical trials. Thus, as a future perspective, we suggest that clinical studies should be conducted with vaccines that have been promising in animal models (e.g., DNA Aβ42 vaccine, AV-1955, and AdPEDI-(Aβ1-6)11).

Scientific and Regulatory Policy Committee Points to Consider*: Approaches to the Conduct and Interpretation of Vaccine Safety Studies for Clinical and Anatomic Pathologists

“…Intramuscular administration of saline causes scant inflammation, often comprised of scattered small aggregates of macrophages or other mononuclear inflammatory cells with or without individual myocyte degeneration or necrosis, edema, hemorrhage, and/or fibrosis (Figure 9). 2 Some antigens alone are highly immunogenic and may cause notable inflammation at the injection site, even when formulated without an adjuvant, although many have changes similar to those identified with saline administration.…”

“…Several therapeutic vaccines are currently being or have been investigated for potential treatment of a diverse number of diseases such as Alzheimer disease, Parkinson disease, and multiple types of cancer. [1][2][3] Vaccines are being developed using a wide variety of modalities, and formulations/therapies may include adjuvants or other immunological modulators to promote the desired immune response.…”

Intracerebral Injection of Extracellular Vesicles from Mesenchymal Stem Cells Exerts Reduced Aβ Plaque Burden in Early Stages of a Preclinical Model of Alzheimer’s Disease

“…The limited knowledge of the etiology of Alzheimer’s has rendered in vain numerous attempts hitherto pursued to find a resolutive treatment that is not simply limited to the alleviation of symptoms. Therefore, a worldwide effort is underway to discover the mechanisms responsible for the disease onset and progression and to find an efficacious therapy, developing either novel treatments [2,3,4] or preventive strategies [5].…”

Feasibility of Identifying Factors Related to Alzheimer’s Disease and Related Dementia in Real-World Data

“…Biomarkers are objective measures that can be used to indicate a patient's medical state accurately and reproducibly, and can be and often used to assess the risk of the patients [191]. We identified 40 unique biomarkers from 24 studies [110,114,155,[192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207][208][209][210]. Among these, 39 were found related to AD, 7 to vascular dementia, and 23 to other types of dementia.…”

“…Among these, 39 were found related to AD, 7 to vascular dementia, and 23 to other types of dementia. Of the 24 studies, 26 biomarkers were found to indicate an increased risk of AD/ADRD [109,110,114,[192][193][194][195][196][197][198][199][200][204][205][206][207][208][209][210], 2 were associated with a decreased risk [155,203], and 2 showed inconsistent results [122,196]. The seven most studied biomarkers included tau, cholesterol, homocysteine, bone mineral density, magnesium, white matter hyperintensities, and vitamin D level.…”