Circulating extracellular vesicle microRNAs associated with adverse reactions, proinflammatory cytokine, and antibody production after COVID-19 vaccination

Yusuke Miyashita; Takanobu Yoshida; Yuriko Takagi; Hirotake Tsukamoto; Ken Takashima; Takahisa Kouwaki; Katsunari Makino; Satoshi Fukushima; Kimitoshi Nakamura; Hiroyuki Oshiumi

doi:10.1038/s41541-022-00439-3

Circulating extracellular vesicle microRNAs associated with adverse reactions, proinflammatory cytokine, and antibody production after COVID-19 vaccination

NPJ Vaccines. 2022 Feb 8;7(1):16. doi: 10.1038/s41541-022-00439-3.

Authors

Yusuke Miyashita^{1

2}, Takanobu Yoshida^{1

2}, Yuriko Takagi¹, Hirotake Tsukamoto^{1

3}, Ken Takashima¹, Takahisa Kouwaki¹, Katsunari Makino⁴, Satoshi Fukushima⁴, Kimitoshi Nakamura², Hiroyuki Oshiumi⁵

Affiliations

¹ Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
² Department of Pediatrics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
³ Division of Clinical Immunology and Cancer Immunotherapy, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁴ Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan.
⁵ Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. oshiumi@kumamoto-u.ac.jp.

Abstract

mRNA-based vaccines have been used globally to eradicate the coronavirus-disease 2019 (COVID-19) pandemic. Vaccine efficacy and adverse reactions depend on immune responses, such as proinflammatory cytokine production and lymphocyte activation. We conducted a prospective cohort study to investigate relationships among specific antibody titers, adverse reactions, proinflammatory cytokine production, and immune-regulatory microRNA (miRNA) levels in serum extracellular vesicles (EVs) after COVID-19 vaccination (BNT162b2). Local adverse reactions after the second dose, such as local pain and swelling, were less correlated with those of systemic symptoms, such as fever and muscle pain, whereas serum TNF-α levels were associated with systemic adverse reactions and with specific antibody titers. Interestingly, EV miR-92a-2-5p levels in sera were negatively correlated with degrees of adverse reactions, and EV miR-148a levels were associated with specific antibody titers. Our data suggest a potential of circulating EV miRNAs as biomarkers for vaccine efficacy and adverse reactions.