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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use
  • Alzheimer Disease / immunology*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy
  • Alzheimer Vaccines / immunology*
  • Alzheimer Vaccines / therapeutic use
  • Amyloid beta-Peptides / immunology*
  • Animals
  • Antibody Formation / immunology*
  • Brain / immunology
  • Brain / metabolism
  • Epitopes, B-Lymphocyte / immunology
  • Female
  • Humans
  • Immunization / methods
  • Inulin / analogs & derivatives
  • Inulin / immunology
  • Mice, Inbred C57BL
  • tau Proteins / immunology*

Substances

  • Adjuvants, Immunologic
  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Epitopes, B-Lymphocyte
  • delta inulin
  • tau Proteins
  • Inulin