Heterologous booster vaccination enhances antibody responses to SARS-CoV-2 by improving Tfh function and increasing B-cell clonotype SHM frequency.

Heterologous prime-boost has broken the protective immune response bottleneck of the COVID-19 vaccines. however, the underlying mechanisms have not been fully elucidated. Here, we investigated antibody responses and explored the response of germinal center (GC) to priming with inactivated vaccines and boosting with heterologous adenoviral-vectored vaccines or homologous inactivated vaccines in mice. Antibody responses were dramatically enhanced by both boosting regimens. Heterologous immunization induced more robust GC activation, characterized by increased Tfh cell populations and enhanced helper function. Additionally, increased B-cell activation and antibody production were observed in a heterologous regimen. Libra-seq was used to compare the differences of S1-, S2- and NTD-specific B cells between homologous and heterologous vaccination, respectively. S2-specific CD19+ B cells presented increased somatic hypermutations (SHMs), which were mainly enriched in plasma cells. Moreover, a heterologous booster dose promoted the clonal expansion of B cells specific to S2 and NTD regions. In conclusion, the functional role of Tfh and B cells following SARS-CoV-2 heterologous vaccination may be important for modulating antibody responses. These findings provide new insights for the development of SARS-CoV-2 vaccines that induce more robust antibody response.

Serum metabolic profiling of coal worker's pneumoconiosis using untargeted lipidomics.

In this work, untargeted lipidomics was employed to analyze the effects of coal dust exposure on serum metabolite profiles. Furthermore, the potential of differential metabolites as novel biomarkers for diagnosis was investigated by binary logistic classification model. Nineteen differential metabolites were found among the three groups. The compounds were enriched in pathways associated with linoleic acid metabolism and pyrimidine metabolism. Fifty-three differential metabolites were found in coal dust-exposed people and CWP patients, and they were mainly enriched in glycerophospholipid metabolism. Three differential metabolites were correlated with lung function values. The diagnostic model, composed of lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0), showed strong discrimination ability between dust-exposed people and CWP patients. The sensitivity, specificity, and AUC values of the model were 0.869, 0.600, and 0.750, respectively. The results suggest that coal worker's pneumoconiosis causes abnormal lipid metabolism in the body. A diagnostic model may aid current CWP diagnostic methods, and lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0) can be used as potential CWP biomarkers. Further study is warranted to validate the findings in larger populations.