作者
Aurélien vander Straeten,Morteza Sarmadi,John L. Daristotle,Maria Kanelli,Lisa H. Tostanoski,Joe Collins,Apurva Pardeshi,Jooli Han,Dhruv Varshney,Behnaz Eshaghi,Johnny Garcia,Timothy A. Forster,Gary Li,Nandita Menon,Sydney L. Pyon,Linzixuan Zhang,Catherine Jacob-Dolan,Olivia Powers,Kevin Hall,Shahad K. Alsaiari,Morris Wolf,Mark W. Tibbitt,Robert Farra,Dan H. Barouch,Róbert Langer,Ana Jaklenec
摘要
Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro. We demonstrate that the resulting MNPs are shelf stable for at least 6 months at room temperature when assessed using a model mRNA construct. Vaccine loading efficiency and microneedle dissolution suggest that efficacious, microgram-scale doses of mRNA encapsulated in lipid nanoparticles could be delivered with a single patch. Immunizations in mice using manually produced MNPs with mRNA encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain stimulate long-term immune responses similar to those of intramuscular administration. Automated fabrication of microneedle patch mRNA vaccines for COVID-19 may improve vaccine access.