Differences in T cell responses to Bordetella Pertussis in adults as a function of whole cell versus acellular childhood vaccination

Abstract In the mid-1990s vaccine-related side effects prompted the replacement of the whole Pertussis (wP) by a new acellular Pertussis vaccine (aP). Unexpectedly, whooping cough cases have recently increased, and the switch to the aP vaccine suspected to underlie this rise in morbidity, despite the use of routine boosters. Here we compared the immune responses to aP boosters in children who received their initial doses with either wP or aP vaccines. The use of ex vivo AIM assays highlighted a Th2 vs Th1/Th17 differential polarization of PT-specific memory CD4+ T cells as a function of childhood vaccination. The nature of the differences was further investigated for memory subset composition, activation, exhaustion marker expression, and transcriptomic profiles. Remarkably, donors originally primed with aP were defective in their ex vivo capacity to expand memory cells following a booster aP immunization and less capable to proliferate in vitro in response to PT epitopes. By contrast antibody responses are boosted in both aP and wP cohorts following IgG subclass distribution. Most recently, we have assessed early immune responses followed aP boosting for the aP and wP cohorts using longitudinal transcriptomics data from PBMC. We have identified several modules of genes that are co-expressed; using cell frequency data from CyTOF we infer modules correlated with specific cell types. Furthermore, we identified certain modules that show differential expression profiles between the two cohorts and are mostly enriched in immune related functions. In conclusion, our data suggest that the original priming after birth with aP and wP vaccines induce different T cell phenotypes associated with long-term T cell polarization.