Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination

Sakiko Toyama; Tomoko Honda; Sadahiro Iwabuchi; Shinichi Hashimoto; Kenzaburo Yamaji; Yuko Tokunaga; Yusuke Matsumoto; Hideya Kawaji; Takashi Miyazaki; Yoshiaki Kikkawa; Michinori Kohara

doi:10.3389/fimmu.2023.1209945

Application of spatial transcriptomics analysis using the Visium system for the mouse nasal cavity after intranasal vaccination

Front Immunol. 2023 Jul 21:14:1209945. doi: 10.3389/fimmu.2023.1209945. eCollection 2023.

Authors

Sakiko Toyama^{1

2}, Tomoko Honda¹, Sadahiro Iwabuchi³, Shinichi Hashimoto³, Kenzaburo Yamaji¹, Yuko Tokunaga¹, Yusuke Matsumoto^{1

4}, Hideya Kawaji⁵, Takashi Miyazaki⁶, Yoshiaki Kikkawa^{2

7}, Michinori Kohara¹

Affiliations

¹ Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
² Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
³ Department of Molecular Pathophysiology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Japan.
⁴ Transboundary Animal Diseases Research Center, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
⁵ Research Center for Genome and Medical Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
⁶ Business Management Department, Toko Yakuhin Kogyo Co., Ltd., Toyama, Japan.
⁷ Deafness Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.

Abstract

Intranasal vaccines that elicit mucosal immunity are deemed effective against respiratory tract infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but their ability to induce humoral immunity characterized by immunoglobulin A (IgA) and IgG production is low. It has been reported that vaccination with a mixture of a viscous base carboxyvinyl polymer (CVP) and viral antigens induced robust systemic and mucosal immune responses. In this study, we analyzed the behavior of immunocompetent cells in the nasal cavity over time by spatial transcriptome profiling induced immediately after antigen vaccination using CVP. We established a method for performing spatial transcriptomics using the Visium system in the mouse nasal cavity and analyzed gene expression profiles within the nasal cavity after intranasal vaccination. Glycoprotein 2 (Gp2)-, SRY-box transcription factor 8 (Sox8)-, or Spi-B transcription factor (Spib)-expressing cells were increased in the nasal passage (NP) region at 3-6 hr after SARS-CoV-2 spike protein and CVP (S-CVP) vaccination. The results suggested that microfold (M) cells are activated within a short period of time (3-6 hr). Subsequent cluster analysis of cells in the nasal cavity showed an increase in Cluster 9 at 3-6 hr after intranasal vaccination with the S-CVP. We found that Il6 in Cluster 9 had the highest log2 fold values within the NP at 3-6 hr. A search for gene expression patterns similar to that of Il6 revealed that the log2 fold values of Edn2, Ccl20, and Hk2 also increased in the nasal cavity after 3-6 hr. The results showed that the early response of immune cells occurred immediately after intranasal vaccination. In this study, we identified changes in gene expression that contribute to the activation of M cells and immunocompetent cells after intranasal vaccination of mice with antigen-CVP using a time-series analysis of spatial transcriptomics data. The results facilitated the identification of the cell types that are activated during the initial induction of nasal mucosal immunity.

Keywords: Visium; carboxyvinyl polymer (CVP); intranasal vaccine; microfold (M) cell; nasal passage (NP); spatial transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
COVID-19*
Gene Expression Profiling
Humans
Interleukin-6
Mice
Nasal Cavity / chemistry
SARS-CoV-2
Transcriptome*
Vaccination / methods

Substances

spike protein, SARS-CoV-2
Interleukin-6
Antibodies, Viral

Grants and funding

This research was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant No. 21K06981), and the Program for the Promotion of Fundamental Studies in Liver Cirrhosis of the Tokyo Metropolitan Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.