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bioRxiv · 10.1101/2021.12.02.471028

Systems immune profiling of variant-specific vaccination against SARS-CoV-2

Peng, L.·Park, J.·Fang, Z.·Zhou, X.·Dong, M.·Xiong, Q.·Lin, C.·Chen, S.
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Abstract

Lipid-nanoparticle(LNP)-mRNA vaccines offer protection against COVID-19. However, multiple variant lineages caused widespread breakthrough infections. There is no report on variant-specific vaccines to date. Here, we generated LNP-mRNAs specifically encoding wildtype, B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses in animal models. All three LNP-mRNAs induced potent antibody responses in mice. However, WT-LNP-mRNA vaccination showed reduced neutralization against B.1.351 and B.1.617; and B.1.617-specific vaccination showed differential neutralization. All three vaccine candidates elicited antigen-specific CD8 and CD4 T cell responses. Single cell transcriptomics of B.1.351-LNP-mRNA and B.1.617-LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induced a systemic increase in reactive CD8 T cell population, with a strong signature of transcriptional and translational machineries in lymphocytes. BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals. These data provide direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.

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Peng, L., Park, J., Fang, Z., Zhou, X., Dong, M., Xiong, Q., Lin, C., Chen, S.. 2021-12-03. Systems immune profiling of variant-specific vaccination against SARS-CoV-2. https://doi.org/10.1101/2021.12.02.471028

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