Michael G. Agadjanyan (United States of America)
Institute for Molecular Medicine
Immunology
I am the Vice President, Professor, and Head of the Department of Molecular Immunology at the Institute for Molecular Medicine (IMM) in Huntington Beach, California. Before coming to IMM, I was Visiting Professor at the University of Pennsylvania (UPENN). After moving in the year 2000 from UPENN to IMM, I have focused my vast experience in vaccine development on the generation and testing of the novel MultiTEP vaccine platform technology for neurodegenerative disorders. More specifically, to overcome serious concerns regarding the limited ability of the elderly to mount an effective immune response to active immunizations, I proposed taking advantage of pre-existing memory CD4+T helper (Th) cells that were generated in response to conventional public health vaccination programs and/or infections with various pathogens. Using this technology, we developed recombinant and nucleic acid-based preventive vaccines targeting pathological amyloid (AV-1959) and tau (AV-1980) separately or together (DUVAX) for Alzheimer’s and different tauopathies. One of these vaccines, AV-1959D is currently in the clinical trial (IND18953), and another, AV-1980R, will be ready for Phase 1 soon. Recently, we completed efficacy studies with MultiTEP platform-based Dementia Lewy Body and Parkinson’s disease preventive vaccine targeting 3 pathological α-synuclein regions simultaneously. Multiple papers have been published on MultiTEP-based vaccines against AD/PD.

Presenter of 1 Presentation

 Conference Calendar

IMMUNOGENICITY OF MULTITEP PLATFORM TECHNOLOGY-BASED TAU VACCINE IN NON-HUMAN PRIMATES: PRELUDE TO CLINICAL TRIALS

Session Name
3300 - SYMPOSIUM: AD THERAPY: TARGETING TAU (ID 28)
Session Type
SYMPOSIUM
Date
Wed, 29.03.2023
Session Time
14:45 - 16:45
Room
ONSITE - HALL F4+F5
Presenter
Lecture Time
15:15 - 15:30

Abstract

Aims

Pathological forms of Tau are directly associated with neurodegeneration and correlate with Alzheimer's Disease (AD) symptoms, progression, and severity. Previously, we have demonstrated the immunogenicity, efficacy, and safety of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A in various mouse models of tauopathies and AD, and rabbits. To support the transition of this preventive vaccine toward human clinical trials, we manufactured the cGMP engineering run AV-1980R. We analyzed its immunogenicity and overall safety in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system.

Methods

AV-1980R was manufactured in a GMP facility from E.coli inclusion bodies. Adult Macaca fascicularis were immunized with adjuvanted vaccines intramuscularly. Antibody titers and C-reactive protein were tested via ELISA. Overall safety was analyzed by monitoring the body weight, temperature, behavior, blood count/chemistry, and C-reactive protein.

Results

We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD, inducing high titers of antibodies. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. No adverse findings attributed to the vaccine were observed in a mouse model of AD, rabbits, and NHP.

Conclusions

Our data support the AV-1980R/A preventive vaccine progression to the first-in-human clinical trial (Dr. Lon Schneider's presentation). We hypothesize that vaccination of cognitively unimpaired people at risk of AD with AV-1980R/A can produce antibodies that will bind PAD of extracellular Tau and reduce the propagation of this early pathological molecule in the brain, thus delaying the onset of dementia.

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