Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core–shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core–shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.
【저자키워드】 Translational research, Vaccines, 【초록키워드】 SARS-CoV-2, Vaccine, COVID-19 vaccine, spike, mRNA vaccine, variant, variants, Spike protein, Protein, T cell, COVID-19 vaccines, stability, mice, non-human primates, inoculation, N501Y, mRNA, humans, vaccine candidate, D614G, Neutralizing, non-human primate, Critical, liver, T cell response, intramuscular, biodistribution, administration, Safe, wild-type SARS-CoV-2, full-length SARS-CoV-2 spike protein, effective, composed, addition, facilitate, unique, effective vaccine, Extensive, full-length SARS-CoV-2, levels of antibody, LPP, packaged, 【제목키워드】 COVID-19, Immunity, mRNA vaccine, biodistribution,