Human immune and gut microbial parameters associated with inter-individual variations in BNT162b2 mRNA vaccine-induced adaptive immunity

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, factors associated with this inter-individual variation are not fully understood. Here, using a systems biology approach based on multi-omics analyses of human blood and stool samples, we identify specific immune cell populations, genes, and gut microbes as novel correlates of Pfizer BNT162b2 mRNA vaccine-induced adaptive immunity. We find that a transcription module related to the AP-1 transcription factor network mediated by Fos, Fosb, and ATF3 is associated with low T-cell responses induced by BNT162b2 vaccination. Fos expression is associated with transcription modules related to baseline immunity, but it is negatively associated with those related to T cell activation upon BNT162b2 mRNA stimulation. Interestingly, the gut microbial fucose/rhamnose degradation pathway is positively correlated with expression of Fos and Atf3, and inversely correlated with BNT162b2-induced T-cell responses. Taken together, these results demonstrate that baseline expression of AP-1 genes, which is associated with the gut microbial fucose/rhamnose degradation pathway, is a key negative correlate of BNT162b2-induced T-cell responses.