Project description:Bordetella pertussis is the etiological agent of whooping cough, a bacterial infection of especially children, which may be fatal without treatment. In frame of studies to investigate putative effects of vaccination on host-pathogen interaction and clonal distribution of strains, in addition to Corynebacterium diphtheriae and Clostridium tetani toxoid vaccines, also whole-cell and acellular pertussis vaccines were analyzed by mass spectrometry.
Project description:Murine lung gene expression responses to primary and secondary infection with Bordetella pertussis. Data were compared to other parameters such as flow cytometry and multiplex immunoassays.
Project description:Since the introduction of new generation pertussis vaccines, resurgence of pertussis is observed in many developed countries. Former whole-cell pertussis vaccines (wP) are able to protect against disease and transmission but have been replaced in several industrialized countries because of their reactogenicity and adverse effects. Current acellular pertussis vaccines (aP), made of purified proteins of Bordetella pertussis, are efficient at preventing disease but fail to induce long-term protection from infection. While the systemic and mucosal T cell immunity induced by the two types of vaccines has been well described, much less is known concerning B cell responses. Taking advantage of an inducible AID-Cre-EYFP fate-mapping mouse model, we sorted and analyzed by scRNAseq the transcriptomic profiles of memory B cells after a combination of prime:boost with the two classes of vaccines. B220+EYFP+GL7-PNA- memory B cells from the draining lymph nodes (dLNs) of tamoxifen-fed mice were FACS sorted 7 weeks after boost, alongside with B220+EYFP+GL7+PNA+ germinal center (GC) B cells and B220+GL7-PNA-EYFP-IgD+ naive B cells as a control population for the unsupervised clustering analysis. Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, PMID: 27693023, with primers described in van den Brink et al. 2017), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).
Project description:Outbreaks of Bordetella pertussis (BP), the causative agent of whooping cough, continue despite broad vaccination coverage and have been increasing since vaccination switched from whole-BP (wP) to acellular BP (aP) vaccines. wP vaccination has been associated with more durable protective immunity and an induced Th1 polarized memory T cell response. Here, a multi-omics approach was applied to profile the immune response of 30 wP and 31 aP-primed individuals and identify correlates of T cell polarization before and after Tdap booster vaccination. We found that transcriptional changes indicating an interferon response on day 1 post-booster along with elevated plasma concentrations of IFN-γ and interferon-induced chemokines that peaked at day 1-3 post-booster correlated best with the Th1 polarization of the vaccine-induced memory T cell response on day 28. Our studies suggest that wP-primed individuals maintain their Th1 polarization through this early memory interferon response. This suggests that stimulating the interferon pathway during vaccination could be an effective strategy to elicit a predominant Th1 response in aP-primed individuals that protects better against infection.
