Ex vivorecapitulation of intramuscular mRNA vaccination with naïve and recall antigens using a human Lymphoid Follicle Chip platform DOI Creative Commons
Yunhao Zhai,

Min‐Wen Ku,

Ka Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Predicting the efficacy and toxicity of intramuscular mRNA vaccines remains challenging. Here, we describe an ex vivo human cell-based model that replicates immune responses to lipid nanoparticle (LNP)-based require injection. Vaccines are administered into a biomimetic muscle module containing skeletal myoblasts antigen-presenting cells (APCs) mimic vaccination, followed by transfer APCs soluble factors microfluidic lymphoid follicle chip (LF Chip) lymphatic drainage. Non-replicating directly induce antigen expression in APCs, whereas self-amplifying cell-APC contact within vaccination module. Transfer LF Chip induces expansion, de novo antigen-specific IgG production against naïve (rabies virus glycoprotein), cytokine release, with varying depending on LNP type. Vaccination chips SARS-COV-2 Spike recall using Moderna Spikevax vaccine generates neutralizing antibodies somatic hypermutation. This platform offers all-human alternative for evaluating vaccine-induced immunity, potentially obviating need non-human primates accelerating development.

Язык: Английский

Ex vivorecapitulation of intramuscular mRNA vaccination with naïve and recall antigens using a human Lymphoid Follicle Chip platform DOI Creative Commons
Yunhao Zhai,

Min‐Wen Ku,

Ka Yang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 17, 2025

Abstract Predicting the efficacy and toxicity of intramuscular mRNA vaccines remains challenging. Here, we describe an ex vivo human cell-based model that replicates immune responses to lipid nanoparticle (LNP)-based require injection. Vaccines are administered into a biomimetic muscle module containing skeletal myoblasts antigen-presenting cells (APCs) mimic vaccination, followed by transfer APCs soluble factors microfluidic lymphoid follicle chip (LF Chip) lymphatic drainage. Non-replicating directly induce antigen expression in APCs, whereas self-amplifying cell-APC contact within vaccination module. Transfer LF Chip induces expansion, de novo antigen-specific IgG production against naïve (rabies virus glycoprotein), cytokine release, with varying depending on LNP type. Vaccination chips SARS-COV-2 Spike recall using Moderna Spikevax vaccine generates neutralizing antibodies somatic hypermutation. This platform offers all-human alternative for evaluating vaccine-induced immunity, potentially obviating need non-human primates accelerating development.

Язык: Английский

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