A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice

Nat Commun. 2022 Jan 27;13(1):549. doi: 10.1038/s41467-022-28197-9.

Abstract

Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being evaluated in human clinical trials. However, the innate mechanisms of 3M-052 have not been fully characterized. Here, we perform flow cytometry, single cell RNA-seq and ATAC-seq to profile the kinetics, transcriptomics and epigenomics of innate immune cells in murine draining lymph nodes following 3M-052-Alum/Ovalbumin immunization. We find that 3M-052-Alum/OVA induces a robust antiviral and interferon gene program, similar to the yellow fever vaccine, which is known to confer long-lasting protection. Activation of myeloid cells in dLNs persists through day 28 and single cell analysis reveals putative TF-gene regulatory programs in distinct myeloid cells and heterogeneity of monocytes. This study provides a comprehensive characterization of the transcriptomics and epigenomics of innate populations in the dLNs after vaccination.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Adjuvants, Immunologic / chemistry*
  • Adjuvants, Immunologic / pharmacology
  • Alum Compounds
  • Animals
  • Antibodies, Viral / immunology
  • Epigenomics
  • Female
  • Humans
  • Immunity, Humoral / immunology*
  • Immunity, Innate* / drug effects
  • Immunization
  • Membrane Glycoproteins / agonists
  • Mice
  • Mice, Inbred C57BL
  • Monocytes
  • Myeloid Cells
  • Ovalbumin
  • Toll-Like Receptor 7 / agonists
  • Toll-Like Receptor 8 / agonists
  • Vaccination
  • Vaccines, Attenuated / immunology*

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Viral
  • Membrane Glycoproteins
  • TLR7 protein, human
  • TLR8 protein, human
  • TLR8 protein, mouse
  • Tlr7 protein, mouse
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Vaccines, Attenuated
  • ovalbumin-alum
  • Ovalbumin