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Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.

ABSTRACT: It is unknown if surface bound toll-like-receptor (TLR) agonists activate cells via density or total molecular number. To answer this question, we developed a TLR agonist surface conjugated polystyrene microparticle (MP) system. Using a library of MPs with varying TLR agonist density and number, we simultaneously observed innate immune cell MP uptake and TNF? expression using ImageStream flow cytometry on a cell by cell basis. The data shows that total TLR number and not density drives cellular activation with a threshold of approximately 10⁵-10⁶ TLR agonists. We believe that this information will be crucial for the design of particulate vaccine formulations.

SUBMITTER: Deak P

PROVIDER: S-EPMC7161694 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.

Deak Peter P Kimani Flora F Cassaidy Brittney B Esser-Kahn Aaron A

Frontiers in immunology 20200409

It is unknown if surface bound toll-like-receptor (TLR) agonists activate cells via density or total molecular number. To answer this question, we developed a TLR agonist surface conjugated polystyrene microparticle (MP) system. Using a library of MPs with varying TLR agonist density and number, we simultaneously observed innate immune cell MP uptake and TNFα expression using ImageStream flow cytometry on a cell by cell basis. The data shows that total TLR number and not density drives cellular ...[more]

PMID: 32328073

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Project description:BackgroundCommunity Health Workers (CHWs) provide basic health screening and advice to members of their own communities. Although CHWs are trained, no CHW programmes have used a formal method to identify the level of achievement on post-training assessments that distinguishes "safe" from "unsafe". Objectives: The aim of this study was to use Ebel method of standard setting for a post-training written knowledge assessment for CHWs in Neno, Malawi.Methods12 participants agreed the definitions of a "just-deployment ready" and an "ideal" CHW. Participants rated the importance and difficulty of each question on a three-point scale and also indicated the proportion of "just-deployment ready" CHWs expected to answer each of the nine question types correctly. Mean scores were used to determine the passing standard, which was reduced by one standard error of measurement (SEM) as this was the first time any passing standard had been employed.The level of agreement across participants' ratings of importance and difficulty was calculated using Krippendorf's alpha. The assessment results from the first cohort of CHW trainees were analysed using classical test theory.FindingsThere was poor agreement between participants on item ratings of both importance and difficulty (Krippendorf's alphas of 0.064 and 0.074 respectively). The pass mark applied to the assessment, following adjustment using the SEM, was 53.3%. Based on this pass mark, 68% of 129 CHW trainees were 'clear passes', 11% 'borderline passes', 9% 'borderline fails' and 12% 'clear fails'.ConclusionsDetermining whether a CHW is deployment-ready is an important, but difficult exercise, as evidenced by a lack of agreement regarding question importance and difficulty. Future exercises should allow more time for training, discussion and modification of ratings. Based on the assessment, most CHWs trained could be considered deployment-ready, but following-up their performance in the field will be vital to validate the pass mark set.

Dataset Information

Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.

Publications

Determining Whether Agonist Density or Agonist Number Is More Important for Immune Activation via Micoparticle Based Assay.

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