Microfluidic Synthesis of Scalable Layer-by-Layer Multiple Antigen Nano-Delivery Platform for SARS-CoV-2 Vaccines
Authors: Yang Xu, Kazuya Masuda, Christine Groso, Rick Hassan, Ziyou Zhou, Kelsey Broderick, Moriya Tsuji, and Christopher Tison
Abstract
The COVID-19 outbreak was a global pandemic with wide-ranging healthcare implications.
Although several mRNA-based vaccines delivered using lipid nanoparticles (LNP) have been approved and demonstrated efficacy at reducing the severity and spread of infection, continued rapid viral evolution and disadvantages currently associated with LNP delivery vehicles (such as toxicity) are driving the design of next-generation SARS-CoV-2 vaccines. Herein, we describe the development of a trimethylated chitosan-based nanoparticle layer-by-layer (LbL) delivery platform for multiple antigens as a scalable and safe COVID-19 vaccine, known as, “LbL-CoV19”. These vaccine candidates have been demonstrated to be biocompatible, safe, and effective at stimulating both humoral and cellular responses for protection in preclinical studies. Preliminary results also indicate that LbL-CoV19 can potentially achieve rapid, long-lasting, and broad protection against the SARS-CoV-2 challenge. The “plug-and-play” platform technology is well suited to preparedness for future pandemics and disease outbreaks.
Fig 1. Scalable plug-and-play Layer-by-Layer (LbL) trimethylated chitosan NP platform for loading of SARS-CoV-2 antigens including Spike protein/peptide (SP) and Non-structural protein/peptide (NSP) as a novel vaccine candidate, (LbL-CoV19). (A) The loaded antigens in each layer could be one or two antigens or open-reading frame accessory protein/peptides (ORF) or one antigen with an adjuvant 7DW8-5; (B) The LBL sustained releases profile of each antigen has been demonstrated in vaccination for potential long-term protection.
Fig 2. NSP Peptide 22 and Spike protein (SP) release profiles over two weeks from 1-step (solid line) and 2-step (dot line) synthesized two-layer LbL-CoV19 vaccine formulation (LbL-CoV-1). Mean (dots) ± SEM is represented for each of the above graphs.
Selected Figures
Keywords: layer-by-layer (LbL); chitosan nanoparticle; SARS-CoV-2; T-cells; sustained releases; adjuvant; Flex-M
Vaccines 2024, 12 (3), 339