Abstract
Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.
Keywords: CP: Immunology; MERS-CoV; SARS-CoV; SARS-CoV-2; cross-reactivity; mRNA vaccine; multiplexed vaccination; multispecies coronavirus vaccine; sequential vaccination; single-cell profiling; systems immunology.
【저자키워드】 SARS-CoV-2, SARS-CoV, mRNA vaccine, MERS-CoV, cross-reactivity, CP: Immunology, systems immunology., single-cell profiling, multiplexed vaccination, multispecies coronavirus vaccine, sequential vaccination, 【초록키워드】 Transcriptome, immunology, coronavirus, COVID-19 vaccine, immune response, vaccination, adaptive, antibody, feasibility, Antibody Response, Delta, Immune profile, animal models, immune, B cell, mRNA, RNA sequencing, vaccine candidate, immune cells, single-cell, Differential gene expression, Coronavirus vaccines, profile, antibody immunity, offer, triplex, antigen-specific antibody, pathogenic coronavirus, vaccination schedule, responses, effective, develop, significantly, activated, increase in, induce, responses against, 【제목키워드】 vaccination, pathogenic coronavirus,