Improving vaccines by understanding plasma cell survival

The primary means of protective immunity coming from vaccines is the formation of long-lived, antibody-producing plasma cells. However, not all vaccines generate long-lived plasma cells: plasma cells formed from mRNA vaccines against Sars-CoV-2 or from influenza split-virus vaccines die within the first few months of the response, whereas other vaccines, such as the measles, mumps and rubella vaccine, generate plasma cells that are effectively immortal. What allows some plasma cells to last forever when others die in short periods? We posit that a survival maxima is programmed into plasma cells. In this project, a student will test the hypothesis that variation in plasma cell lifespan is set by the coordinate activity of survival proteins. Variation in expression amounts of anti-apoptotic proteins will be evaluated in short- and long-lived plasma cells. The student will use recently developed plasma cell cre-lox timestamping mice to genetically mark plasma cells with an indelible reporter, and examine fates of cells with specific survival programs over time. With these data, the ensemble survival potential of plasma cells formed by different vaccination regimes will be derived, to provide a new framework in which survival stratification may be viewed. The student will gain experience with high dimensional flow cytometry, mouse handling, cutting-edge cellular immunology techniques, mathematical modelling and repertoire analysis and single-cell RNAseq.