Summary: Researchers report a promising vaccine formulation that targets the pathological proteins linked to Alzheimer’s disease, offering potential for both prevention and treatment.
Source: Flinders University.
As global cases of Alzheimer’s disease increase, the search for an effective vaccine and treatments has become urgent.
Researchers in the United States and Australia have announced a significant advance toward a vaccine that targets the abnormal beta-amyloid and tau proteins central to Alzheimer’s disease (AD), the leading cause of dementia in older adults.
New findings published in the journal Scientific Reports describe work led by Flinders University researchers in collaboration with the Institute of Molecular Medicine (IMM) and the University of California, Irvine (UCI). Their team has developed vaccine formulations that provoke strong immune responses against the pathological forms of Aβ (beta-amyloid) and tau proteins associated with AD.
The global burden of dementia is rising rapidly. With an estimated 48 million people living with dementia in 2015 and more than 7.5 million new cases each year, Alzheimer’s is a growing cost to health systems worldwide. The World Health Organization has projected the total global societal cost of dementia-related care at over US$600 billion annually.
“If pre-clinical trials are successful, we could be on the path to one of the most important medical developments in recent history within three to five years,” says Professor Nikolai Petrovsky of Flinders University School of Medicine, who also directs the vaccine company Vaxine Pty Ltd.
Professor Petrovsky notes that ageing populations and the rising prevalence of type 2 diabetes—now recognized as a major risk factor for Alzheimer’s disease—are likely to increase the future number of dementia cases, heightening the need for effective preventive and therapeutic options.
Responding to this public-health challenge, the US Congress has increased funding for Alzheimer’s research. The National Institutes of Health (NIH) and the Alzheimer’s Association have supported development of a universal vaccine platform called MultiTEP, designed to target the hallmark pathological molecules: aberrant forms of Aβ and tau.
While β-amyloid is often considered a primary driver of AD pathology, accumulation of pathological tau correlates strongly with cognitive decline. The research team evaluated vaccine candidates that target Aβ, tau, or both, using the MultiTEP immunogenic platform combined with several adjuvants. The most promising adjuvant in their studies was Advax™ (AdvaxCpG), a delta inulin-based technology developed by Vaxine Pty Ltd that enhances immune responses while maintaining a favorable safety profile.
Professor David Cribbs of the UCI Institute for Memory Impairments and Neurological Disorders (UCI MIND) said the combined anti-amyloid and anti-tau approach formulated with Advax showed potential for both preventive vaccination in at-risk individuals and therapeutic use for patients already showing signs of disease.
IMM’s Professor Michael Agadjanyan explained that MultiTEP-based vaccines are designed to avoid harmful auto-reactive cellular immune responses while still generating high-affinity antibodies that recognize amyloid and tau aggregates found in the brains of AD patients.
Associate Professor Anahit Ghochikyan, co-author of the study, highlighted a possible staged vaccination strategy: immunize individuals in early stages of AD—or even healthy people at elevated risk—with the anti-Aβ vaccine, and if disease progresses, administer an anti-tau vaccine to strengthen protection and therapeutic effect.
The collaborative team, which includes scientists from IMM, UCI and the University of Southern California, is conducting non-clinical safety and toxicology studies with partner companies to meet US regulatory requirements for an Investigational New Drug (IND) application. After these pre-clinical safety assessments are completed, the vaccines will proceed to human trials to test immunogenicity and efficacy.
Vaxine Pty Ltd, a partner on the project, is known for its work in vaccine development, including contributions during the 2009 swine flu pandemic. Vaxine’s Advax adjuvant technology is being applied here to maximize antibody responses to the MultiTEP-based vaccines.
Funding: Development of the Advax adjuvant and related research has been supported by the US National Institutes of Health (NIH), which funds novel adjuvant research aimed at improving vaccine effectiveness.
Source: Shoshana Wodinsky – Flinders University
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Full open-access research titled “Alzheimer’s disease AdvaxCpG-adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules” by Hayk Davtyan et al., published online July 1, 2016. The study reports pre-clinical results assessing vaccine immunogenicity and antibody responses against pathological Aβ and tau species.
MLA: Flinders University. “Progress in World’s First Alzheimer’s Vaccine.” NeuroscienceNews, 14 July 2016.
APA: Flinders University. (2016, July 14). Progress in World’s First Alzheimer’s Vaccine. NeuroscienceNews. Retrieved July 14, 2016.
Chicago: Flinders University. “Progress in World’s First Alzheimer’s Vaccine.” NeuroscienceNews. (accessed July 14, 2016).
Abstract
Alzheimer’s disease AdvaxCpG-adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules
The study evaluates vaccines based on the MultiTEP platform that target B cell epitopes of Aβ (AV-1959R), tau (AV-1980R), or both (AV-1953R). Because high antibody titers are likely required for vaccine efficacy in AD, the team formulated these constructs with several adjuvants and compared immune responses in pre-clinical models. AV-1959R combined with AdvaxCpG induced the strongest cellular and humoral responses. The dual-epitope vaccine AV-1953R, or a combination of AV-1959R and AV-1980R with AdvaxCpG, produced robust antibody responses to multiple forms of both Aβ and tau pathological molecules. Anti-Aβ titers after AV-1953R were comparable to AV-1959R-based approaches, while anti-tau titers were higher when AV-1980R was given alone or in combination. Computational 3D modeling helped explain differences in immunogenicity among constructs. Overall, AV-1959R and AV-1980R formulated with AdvaxCpG were identified as promising candidates for continued pre-clinical testing and eventual human clinical trials.
The research team includes Hayk Davtyan, Karen Zagorski, Harinda Rajapaksha, Armine Hovakimyan, Arpine Davtyan, Irina Petrushina, Konstantin Kazarian, David H. Cribbs, Nikolai Petrovsky, Michael G. Agadjanyan, and Anahit Ghochikyan. Published online July 1, 2016.