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Sci Rep. 2016 Jul 1;6:28912. doi: 10.1038/srep28912.

Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules.

Author information

1
Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
2
Vaxine Pty Ltd, Flinders Medical Center, Bedford Park, Adelaide, 5042, Australia.
3
Department of Diabetes and Endocrinology, Faculty of Medicine, Flinders University, Adelaide, 5042, Australia.
4
The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, 92697, USA.
5
Department of Neurology, University of California Irvine, Irvine, California, 92697, USA.

Abstract

Although β-amyloid (Aβ) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials.

PMID:
27363809
PMCID:
PMC4929459
DOI:
10.1038/srep28912
[Indexed for MEDLINE]
Free PMC Article

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