Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced immunity

• Published in: Communications biology Vol. 6; no. 1; pp. 368 - 14
• Main Authors: Hirota, Masato, Tamai, Miho, Yukawa, Sachie, Taira, Naoyuki, Matthews, Melissa M., Toma, Takeshi, Seto, Yu, Yoshida, Makiko, Toguchi, Sakura, Miyagi, Mio, Mori, Tomoari, Tomori, Hiroaki, Tamai, Osamu, Kina, Mitsuo, Sakihara, Eishin, Yamashiro, Chiaki, Miyagi, Masatake, Tamaki, Kentaro, Wolf, Matthias, Collins, Mary K., Kitano, Hiroaki, Ishikawa, Hiroki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 38/1; 38/39; 38/91; 631/250/2152/1566/1618; 631/250/590/2293; Activator protein 1; Adaptive immunity; Antibodies, Viral; Biodegradation; Biology; Biomedical and Life Sciences; BNT162 Vaccine; Coronaviruses; COVID-19 - prevention & control; COVID-19 Vaccines; Gastrointestinal Microbiome; Gene expression; Humans; Life Sciences; Lymphocytes T; Monocytes; mRNA vaccines; Prostaglandin E2; RNA, Messenger - genetics; SARS-CoV-2 - genetics; Severe acute respiratory syndrome coronavirus 2; Transcription activation; Transcription Factor AP-1; Transcription factors; Variation
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-04755-9

COVID-19 mRNA vaccines induce protective adaptive immunity against SARS-CoV-2 in most individuals, but there is wide variation in levels of vaccine-induced antibody and T-cell responses. However, the mechanisms underlying this inter-individual variation remain unclear. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identified several factors that are associated with COVID-19 vaccine-induced adaptive immune responses. BNT162b2-induced T cell response is positively associated with late monocyte responses and inversely associated with baseline mRNA expression of activation protein 1 (AP-1) transcription factors. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with mRNA expression of AP-1, as well as a gene encoding an enzyme producing prostaglandin E2 (PGE2), which promotes AP-1 expression, and inversely correlated with BNT162b2-induced T-cell responses. These results suggest that baseline AP-1 expression, which is affected by commensal microbial activity, is a negative correlate of BNT162b2-induced T-cell responses. Multi-omics analyses of human blood and stool samples reveal that baseline AP-1 expression, which is affected by commensal microbial activity, is negatively associated with BNT162b2-induced T-cell responses.