ProMIS Neurosciences Inc PMN

RE:RE:PMN to Present at the 2022 International AD/PDTM Conference

[Speyeder999]

I also  noticed that our SAB chair, Rudy Tanzi will be presenting at this event (although not under the Promis banner). 

Below is what Dr. Kaplan will be presenting.

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

Lecture Time

09:20 AM - 09:35 AM

Presenter

• Johanne Kaplan (United States of America)

• 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.