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

Audrey Lee, Madeleine K. D. Scott, Florian Wimmers, Prabhu S. Arunachalam, Wei Luo, Christopher B. Fox, Mark Tomai, Purvesh Khatri () and Bali Pulendran ()
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Audrey Lee: Stanford University School of Medicine, Stanford University
Madeleine K. D. Scott: Stanford University School of Medicine, Stanford University
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
Bali Pulendran: Stanford University School of Medicine, Stanford University

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-28197-9

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