Abstract
Lipid nanoparticle (LNP)-mRNA vaccines offer protection against COVID-19; however, multiple variant lineages caused widespread breakthrough infections. Here, we generate LNP-mRNAs specifically encoding wild-type (WT), B.1.351, and B.1.617 SARS-CoV-2 spikes, and systematically study their immune responses. All three LNP-mRNAs induced potent antibody and T cell responses in animal models; however, differences in neutralization activity have been observed between variants. All three vaccines offer potent protection against in vivo challenges of authentic viruses of WA-1, Beta, and Delta variants. Single-cell transcriptomics of WT- and variant-specific LNP-mRNA-vaccinated animals reveal a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induces a systemic increase of reactive CD8 T cells and altered gene expression programs in B and T lymphocytes. BCR-seq and TCR-seq unveil repertoire diversity and clonal expansions in vaccinated animals. These data provide assessment of efficacy and direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.
Keywords: B.1.351; B.1.617; B.1.617.2; BCR; Beta variant; Delta variant; LNP-mRNA; TCR; lipid nanoparticle; neutralization; single-cell profiling; systems immunology; variant-specific COVID-19 vaccine.
【저자키워드】 B.1.351, neutralization, B.1.617.2, delta variant, B.1.617, Beta variant, TCR, systems immunology, Lipid nanoparticle, BCR, LNP-mRNA, single-cell profiling, variant-specific COVID-19 vaccine., 【초록키워드】 viruses, mRNA vaccination, Efficacy, Vaccine, Single-cell transcriptomics, COVID-19 vaccine, vaccination, Gene Expression, Lymphocytes, antibody, B.1.351, T cells, neutralization, variant, Delta, B.1.617.2, animal models, delta variant, virus, variants, mRNA vaccines, T cell, mRNA, immune responses, immune profiling, B.1.617, T cell responses, Lineage, breakthrough infections, Beta, T lymphocytes, Beta variant, in vivo, single-cell, T cell response, Delta variants, Lipid, CD8 T cell, clonal expansions, These data, neutralization activity, wild-type, offer, immune cell populations, widespread, reactive, B and T lymphocytes, SARS-CoV-2 spikes, caused, generate, induce, immune cell population, 【제목키워드】 SARS-CoV-2, immune response, vaccination, in vivo, induce,