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

Author

Listed:
  • Audrey Lee

    (Stanford University School of Medicine, Stanford University)

  • Madeleine K. D. Scott

    (Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine)

  • Florian Wimmers

    (Stanford University School of Medicine, Stanford University)

  • Prabhu S. Arunachalam

    (Stanford University School of Medicine, Stanford University)

  • Wei Luo

    (Indiana University School of Medicine)

  • Christopher B. Fox

    (Infectious Disease Research Institute)

  • Mark Tomai

    (3M Corporate Research and Materials Lab)

  • Purvesh Khatri

    (Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine)

  • Bali Pulendran

    (Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University
    Stanford University School of Medicine, Stanford University)

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.

Suggested Citation

  • Audrey Lee & Madeleine K. D. Scott & Florian Wimmers & Prabhu S. Arunachalam & Wei Luo & Christopher B. Fox & Mark Tomai & Purvesh Khatri & Bali Pulendran, 2022. "A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28197-9
    DOI: 10.1038/s41467-022-28197-9
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