Immunization Therapy for Alzheimer Disease: A Comprehensive Review of Active Immunization Strategies

Tabira, Takeshi

doi:10.1620/tjem.220.95

Cited by 59 publications

(40 citation statements)

References 65 publications

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“…55 As a result of these characteristics of AD, passive immunotherapy requires a production system that is highly versatile. A short expression cycle from DNA to protein as well as an ease of scalability to very large production runs is essential.…”

Section: Antibodies and Vaccinesmentioning

confidence: 99%

Emerging antibody products and Nicotiana manufacturing

2011

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Section: Antibodies and Vaccinesmentioning

confidence: 99%

Emerging antibody products and Nicotiana manufacturing

2011

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“…Thirdly, we need biomarkers that support evaluation of therapeutic effects. Several classes of amyloidreducing drugs such as γ -secretase inhibitors (De Strooper et al 2010) and amyloid immunization therapy (Tabira 2010) might become available in the near future. For the development of these therapeutic drugs, development of methodology to objectively access "decrease or removal of amyloid" is necessary.…”

Section: Biomarkers With a Bridging Role In The Paradigm Shiftmentioning

confidence: 99%

Geriatric Medicine, Japanese Alzheimer's Disease Neuroimaging Initiative and Biomarker Development

Arai

Okamura

Furukawa

et al. 2010

Tohoku J. Exp. Med.

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Geriatric medicine is an independent internal medicine division that is specialized for management of medical problems of elderly people. Despite a fact that elderly people appear healthy, a variable latent organ dysfunction may be present due to a limited residual capacity. A condition referred to as geriatric syndrome is a complex and multiorgan disease especially suffered by elderly people. The geriatric syndrome consists of more than 50 medical conditions such as dementia, depression, delirium, pneumonia, urinary incontinence, osteoporosis and fractures as well as malnutrition, sarcopenia, skin ulceration and renal failure. Importantly, these clinical conditions often occur in combination rather than separately. As illustrated in Fig.1, most important functions which support independence of life in later years are: 1) Thinking and judgments; 2) Eating and swallowing; and 3) Standing and walking. Loss of these basic functions alone or in combination will directly lead to devastating health implications and reduced quality of life. Disturbance of cognitive ability manifests as dementia. Impairment of ordered oropharyngeal functions causes a disturbed swallowing or dysphasia followed by development of aspiration pneumonia. Failure of standing and walking results in repeated falls and fractures. -all being hardly present before the age of 65 but highly prevalent over the age of 75. Moreover, these problems not merely occur in separate occasions but they also are inter-related each other. For example, people with advanced dementia are likely to develop eating problems and aspiration Wada et al. 2001;Mitchell et al.

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“…The first clinical trial AN-1792, which evaluated an Aβ1-42/QS-21 vaccine, was halted in phase II when about 6% of the patients developed meningoencephalitis (8). Although the exact mechanism that led to acute brain inflammation in this clinical trial remains unclear, it is believed that encephalitis arose from an autoimmune reaction triggered by a vaccine directed against the abundant self-protein Aβ coupled to the strong adjuvant QS-21, thus favoring pro-inflammatory T helper 1 (Th1) immune responses (9). In this context, second generation anti-Aβ vaccines were designed to prevent T-cell responses during anti-Aβ immunization.…”

Section: Introductionmentioning

confidence: 99%

A Modification-Specific Peptide-Based immunization Approach Using CRM197 Carrier Protein: Development of a Selective Vaccine Against Pyroglutamate Aβ Peptides

Zhao

Chandakkar

Acker

et al. 2016

Mol Med

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Strategies aimed at reducing cerebral accumulation of the amyloid-β (Aβ) peptides have therapeutic potential in Alzheimer's disease (AD). Aβ immunization has proven to be effective at promoting Aβ clearance in animal models but adverse effects have hampered its clinical evaluation. The first anti-Aβ immunization clinical trial, which assessed a full-length Aβ1-42 vaccine, increased the risk of encephalitis most likely because of autoimmune pro-inflammatory T helper 1 (Th1) response against all forms of Aβ. Immunization against less abundant but potentially more pathologically relevant Aβ products, such as N-terminally-truncated pyroglutamate-3 Aβ (AβpE3), could provide efficacy and improve tolerability in Aβ immunotherapy. Here, we describe a selective vaccine against AβpE3, which uses the diphtheria toxin mutant CRM197 as carrier protein for epitope presentation. CRM197 is currently used in licensed vaccines and has demonstrated excellent immunogenicity and safety in humans. In mice, our AβpE3:CRM197 vaccine triggered the production of specific anti-AβpE3 antibodies that did not cross-react with Aβ1-42, non-cyclized AβE3, or N-terminally-truncated pyroglutamate-11 Aβ (AβpE11). AβpE3:CRM197 antiserum strongly labeled AβpE3 in insoluble protein extracts and decorated cortical amyloid plaques in human AD brains. AntiAβpE3 antibodies were almost exclusively of the IgG1 isotype, suggesting an anti-inflammatory Th2 response bias to the AβpE3:CRM197 vaccine. To the best of our knowledge, this study shows for the first time that CRM197 has potential as a safe and suitable vaccine carrier for active and selective immunization against specific protein sequence modifications or conformations, such as AβpE3.

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Immunization Therapy for Alzheimer Disease: A Comprehensive Review of Active Immunization Strategies

Cited by 59 publications

References 65 publications

Emerging antibody products and Nicotiana manufacturing

Emerging antibody products and Nicotiana manufacturing

Geriatric Medicine, Japanese Alzheimer's Disease Neuroimaging Initiative and Biomarker Development

A Modification-Specific Peptide-Based immunization Approach Using CRM197 Carrier Protein: Development of a Selective Vaccine Against Pyroglutamate Aβ Peptides

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