title: 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.
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.
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Hayk
authors.initials: H
authors.lastname: Davtyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Zagorski
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Center, Bedford Park, Adelaide, 5042, Australia.|Department of Diabetes and Endocrinology, Faculty of Medicine, Flinders University, Adelaide, 5042, Australia.
authors.forename: Harinda
authors.initials: H
authors.lastname: Rajapaksha
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Armine
authors.initials: A
authors.lastname: Hovakimyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Arpine
authors.initials: A
authors.lastname: Davtyan
authors.affiliation: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, 92697, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Petrushina
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kazarian
authors.affiliation: The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, 92697, USA.|Department of Neurology, University of California Irvine, Irvine, California, 92697, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Cribbs
authors.affiliation: Vaxine Pty Ltd, Flinders Medical Center, Bedford Park, Adelaide, 5042, Australia.|Department of Diabetes and Endocrinology, Faculty of Medicine, Flinders University, Adelaide, 5042, Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.|The Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, California, 92697, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Agadjanyan
authors.affiliation: Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, 92647, USA.
authors.forename: Anahit
authors.initials: A
authors.lastname: Ghochikyan
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D023582:Alzheimer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007444:Inulin / Q000031:analogs & derivatives / Q000276:immunology; D008810:Mice, Inbred C57BL; D016875:tau Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D023582:Alzheimer Vaccines; D016229:Amyloid beta-Peptides; D018985:Epitopes, B-Lymphocyte; C576871:delta inulin; D016875:tau Proteins; D007444:Inulin