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A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease.

ABSTRACT: Traditional vaccination against infectious diseases relies on generation of cellular and humoral immune responses that act to protect the host from overt disease even though they do not induce sterilizing immunity. More recently, attempts have been made with mixed success to generate therapeutic vaccines against a wide range of noninfectious diseases including neurodegenerative disorders. After the exciting first report of successful vaccine prevention of progression of an Alzheimer's disease (AD) animal model in 1999, various epitope-based vaccines targeting amyloid beta (A?) have proceeded to human clinical trials, with varied results. More recently, AD vaccines based on tau protein have advanced into clinical testing too. This review seeks to put perspective to the mixed results obtained so far in clinical trials of AD vaccines and discusses the many pitfalls and misconceptions encountered on the path to a successful AD vaccine, including better standardization of immunologic efficacy measures of antibodies, immunogenicity of platform/carrier and adjuvants.

SUBMITTER: Agadjanyan MG

PROVIDER: S-EPMC4630107 | biostudies-other | 2015 Oct

REPOSITORIES: biostudies-other

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A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease.

Agadjanyan Michael G MG Petrovsky Nikolai N Ghochikyan Anahit A

Alzheimer's & dementia : the journal of the Alzheimer's Association 20150717 10

Traditional vaccination against infectious diseases relies on generation of cellular and humoral immune responses that act to protect the host from overt disease even though they do not induce sterilizing immunity. More recently, attempts have been made with mixed success to generate therapeutic vaccines against a wide range of noninfectious diseases including neurodegenerative disorders. After the exciting first report of successful vaccine prevention of progression of an Alzheimer's disease (A ...[more]

PMID: 26192465

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Project description:ObjectiveThe optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA) are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.MethodsThe model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection) using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.ResultsThe model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84) and incidence of invasive disease (mean R2 0.89). The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.DiscussionWe have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the feasibility and benefits of MenA vaccination strategies.

Dataset Information

A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease.

Publications

A fresh perspective from immunologists and vaccine researchers: active vaccination strategies to prevent and reverse Alzheimer's disease.

Similar Datasets

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