Human immune and gut microbial parameters associated with inter-individual variations in COVID-19 mRNA vaccine-induced 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, 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.journal articl

Pillar[6]arene acts as a biosensor for quantitative detection of a vitamin metabolite in crude biological samples

ビタミン代謝物を迅速定量できる超分子バイオセンサーを開発. 京都大学プレスリリース. 2020-12-09.Metabolic syndrome is associated with obesity, hypertension, and dyslipidemia, and increased cardiovascular risk. Therefore, quick and accurate measurements of specific metabolites are critical for diagnosis; however, detection methods are limited. Here we describe the synthesis of pillar[n]arenes to target 1-methylnicotinamide (1-MNA), which is one metabolite of vitamin B3 (nicotinamide) produced by the cancer-associated nicotinamide N-methyltransferase (NNMT). We found that water-soluble pillar[5]arene (P5A) forms host–guest complexes with both 1-MNA and nicotinamide, and water-soluble pillar[6]arene (P6A) selectively binds to 1-MNA at the micromolar level. P6A can be used as a “turn-off sensor” by photoinduced electron transfer (detection limit is 4.38 × 10−6 M). In our cell-free reaction, P6A is used to quantitatively monitor the activity of NNMT. Moreover, studies using NNMT-deficient mice reveal that P6A exclusively binds to 1-MNA in crude urinary samples. Our findings demonstrate that P6A can be used as a biosensor to quantify 1-MNA in crude biological samples

マウス胸腺の脂肪細胞分化過程の速度論による解析

The differential process of adipocytes was investigated in the thymus and spleen of BALB/c mice by the real time PCR method. The transcriptions of PPARγ (PP) ,adiponectin (Ad) and resistin (Re) were considered as indications of differential stages of adipocytes and the transcription ratios, log Ad/PP and log Re/PP , were measured. These logarithmic ratios increased rapidly, at the border between fetal stage and neonatal, from negative value to positive in the thymus and to nearly 0 in the spleen. Subsequently, they were remained virtually constant throughout the experimental period. Kinetics was applied to the differential model of adipocytes in which the quantity of each transcription was assumed to be proportional to the cell number, and the changes of log Ad/PP and log Re/PP with age were interpreted successfullyBALB/cマウスの胸腺および脾臓での脂肪細胞の分化過程を,PPARγ(PP)に対するアディポネクチン(Ad),およびレジスチン(Re)の転写量を指標として,リアルタイムPCR法により検討した。加齢に伴い成熟脂肪細胞が増加してくる胸腺においては,アディポネクチンおよびレジスチンの転写量は,胎生期にはPPARγ の転写量より少なかったが,出生を境に急激に増大し,PPARγ の転写量の数十倍となり,その後ほぼ一定となった。成熟した脂肪細胞が認められない脾臓では,アディポネクチンおよびレジスチンの転写量は,出生を境に増大し,PPARyの転写量とほぼ等しくなった。各遺伝子の転写量は細胞数に比例すると仮定し,脂肪細胞系列の幹細胞を考えることにより,これらの結果を,速度論により説明することができた

Diffuse Alveolar Hemorrhage Developing Immediately after Immunosuppressive Treatments in a Patient with Granulomatosis with Polyangiitis Who Had Pulmonary Nodules

A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) based on the detection of high myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), vasculitis and granulomas in a lung biopsy specimen and crescentic glomerulonephritis in a kidney biopsy specimen. Soon after the initiation of intravenous methylprednisolone pulse therapy (mPSL pulse) and intravenous cyclophosphamide pulse therapy (IVCY), the patient experienced cough and hemoptysis. Based on emerging anemia and bilateral diffuse lung consolidation on computed tomography, we judged that diffuse alveolar hemorrhage (DAH) was complicated by GPA. The patient’s DAH improved following additional mPSL pulse and IVCY. Physicians should be aware of the possible occurrence of DAH, even when a patient’s symptoms improve after mPSL pulse and IVCY