Variant-specific vaccination induces systems immune responses and potent in vivo protection against SARS-CoV-2

Cell Rep Med. 2022 May 17;3(5):100634. doi: 10.1016/j.xcrm.2022.100634. Epub 2022 Apr 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Immunity
  • Liposomes
  • Nanoparticles
  • RNA, Messenger / genetics
  • SARS-CoV-2*
  • Vaccination


  • Antibodies, Neutralizing
  • COVID-19 Vaccines
  • Lipid Nanoparticles
  • Liposomes
  • RNA, Messenger

Supplementary concepts

  • SARS-CoV-2 variants