ProMIS Neurosciences
R&D
Dr. Kaplan has over 25 years of experience in drug development in the biotechnology industry. She currently serves as Chief Development Officer with ProMIS Neurosciences, a company developing therapies for neurodegenerative disorders. Prior to these appointments, Dr. Kaplan held positions of increasing responsibility at Genzyme Corporation, most recently as a Vice President of Research, in the fields of neuroimmunology, cancer immunotherapy, gene therapy, and autoimmunity. She led the work of the Research Team supporting the approval and launch of Lemtrada and Aubagio for the treatment of relapsing-remitting multiple sclerosis. Prior to joining Genzyme, she was an Associate Immunopathologist at SmithKline Beecham where she established an immunotoxicology program. Her work has resulted in over 70 scientific publications and multiple patents. Dr. Kaplan holds a Ph.D. in Microbiology & Immunology from McGill University in Montreal, Canada and conducted post-doctoral studies at the Albert Einstein College of Medicine in New York.

Presenter of 1 Presentation

OPTIMIZING VACCINE DESIGN FOR ALZHEIMER’S DISEASE: SELECTIVE TARGETING OF COMPUTATIONALLY-DERIVED CONFORMATIONAL B CELL EPITOPES OF SOLUBLE AMYLOID-BETA TOXIC OLIGOMERS

Session Type
SYMPOSIUM
Date
Sun, 20.03.2022
Session Time
09:05 AM - 11:05 AM
Room
ONSITE: 113
Lecture Time
09:20 AM - 09:35 AM

Abstract

Aims

Design an optimal amyloid-beta (Abeta) vaccine to elicit antibodies selective for toxic Abeta oligomers (ABO) without inducing potentially detrimental B or T cell reactivity to normal Abeta.

Methods

A conformational B cell epitope previously determined to elicit antibodies selective and protective against toxic ABO (cyclized HHQK peptide; Gibbs et al, Scientific Reports, 2018), was coupled to KLH as a carrier protein to provide T helper epitopes. Mice received 2 immunizations with the conjugate in 3 different adjuvant formulations (alum, Emulsigen, TriAdj). Serum titers of total IgG, IgG1 and IgG2a antibodies to the peptide epitope were measured by ELISA. T helper type 1 (Th1) and type 2 (Th2) responses to the peptide and to KLH were evaluated by ELISPOT analysis of splenic lymphocytes.

Results

A robust antibody response against the conformational peptide epitope was observed with all 3 adjuvants. Alum gave rise to a predominantly IgG1 response while Emulsigen and TriAdj produced a more comparable IgG1/IgG2a response. ELISPOT analysis showed a lack of Th1 (interferon-gamma) or Th2 (IL-5) cytokine production in response to stimulation with the ABO epitope thereby confirming that the peptide only contains a B cell epitope. T cell help was provided by the carrier and stimulation with KLH induced Th2-biased cytokine production.

Conclusions

A vaccine consisting of an ABO-restricted conformational B cell epitope conjugated to KLH for T cell help successfully induced an antibody response to the B cell epitope without eliciting a potentially inflammatory Abeta-directed T helper response. This vaccine configuration has the potential for optimal safety and efficacy.

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