Bordetella pertussis vaccine composition drives hematopoietic stem and progenitor cell expansion and immune response during vaccination and subsequent challenge

Pertussis is a re-emerging infectious disease world-wide. It is hypothesized that current acellular vaccines (ACVs) wane in efficacy each year after immunization. We hypothesized that whole cell vaccines (WCVs) induce hematopoietic stem and progenitor cell (HSPC) expansion and differentiation processes necessary for life-long protection. While HSPC innate immune signaling and expansion play a critical role in directing immune response to infection, their role in vaccine efficacy is unclear. To test our hypothesis, we assessed bone marrow (BM) HSPC frequency, peripheral blood composition, and immune cell proportions in the spleen and thymus upon vaccination. We find that the BM Lineage-Sca1+cKit+ (LSK) cell population undergoes progressive expansion in WCV mice when compared to ACV and PBS-injected control mice. Additionally, peripheral white blood cells and spleen size increase in WCV mice, suggesting that BM cells mobilize to the blood and spleen, where extramedullary hematopoiesis can occur. Upon infection, myeloid cells have been demonstrated to leave the spleen, enter infected tissues, and produce cytokines that favor the generation of Th1 cells. Occurring more rapidly in WCV mice, LSK cell frequency increases and spleen size decreases upon B. pertussis challenge in both WCV and PBS-injected mice when compared to ACV mice. WCV mice exhibit increased peripheral blood monocytes, neutrophils, and lymphocytes when compared to other groups. Taken together, our data suggest that HSPC expansion, differentiation, and mobilization upon WCV immunization may prime the host to better respond to pathogen, and that ACVs formulated with adjuvants that stimulate HSPC expansion, such as TLR4 agonists, may enhance vaccine efficacy.