Transcriptomic profile of circulating CD4+ T cells from TCM and TEM memory compartments from donors vaccinated at birth either with whole or acellular Pertussis vaccine
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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, particularly in teenagers. Here we compared individuals born before 1995 and vaccinated in infancy with wP, with individuals born in 1996 or later and vaccinated with aP in infancy. Remarkably, we detected differences in the two populations in response to a contemporary aP booster, despite the fact that the original aP or wP priming occurred more than 18 years previously. The nature of the differences in T cells between aP and wP original priming was further investigated by evaluation of memory subset composition in respect to function, activation and exhaustion expression protein markers and RNA transcriptomic profiles of the PT-specific T cells from aP vs. wP donors. Transcriptomic profile of circulating CD4+ T cells from TCM and TEM memory compartments from donors vaccinated at birth either with whole or acellular Pertussis vaccine. All donors were boosted with the aP vaccine 1-3 months before the PBMCs were collected.
Project description:System level view of the vaccine induced immune response to identify perturbations at the level of gene expression in whole PBMC specifically in response to pertussis antigenic challenge in vivo (Tdap vaccine boost) as a proxy of infectious challenge, and whether this response differed in aP vs. wP primed individuals 15 years or more after the original vaccination. RNA-Seq analysis on PBMC samples collected longitudinally at baseline and following Tdap booster vaccination. For this purpose, we recruited addults primed with either aP and wP and proceeded to booster vaccination with aP. PBMCs were collected for transcriptomics at 0 days post boost (baseline) followed by 1, 3, 7 and 14 days post boost. Bulk PBMC RNA sequencing was performed for 39 donors with 5 timepoints (0, 1, 3, 7 and 14 days post boost) +1 donor with 3 timepoints (0, 1 and 3 days post boost)
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.
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:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, pertussis antibody levels decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which may be associated with humoral responses, we analyzed changes in gene expression.
Project description:Transcriptomic profile of circulating CD4+ T cells from TCM and TEM memory compartments from donors vaccinated at birth either with whole or acellular Pertussis vaccine
Project description:These 14 samples originate from peripheral blood mononuclear cells (PBMC) from donors at different times after they were vaccinated with the YF-17D vaccine.
Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine
Project description:The project includes sequencing data of isolated PBMCs extracted from donors that received the MMR vaccine and donors that received placebo, both containg samples before and after the vaccine.
In total, 6 MMR-vaccinated and 6 Placebo donors for both timepoints were included in the scRNAseq data.
In total, 12 MMR-vaccinated and 12 Placebo donors for both timepoints were included in the scATACseq data.
The main goal of the project is studying the non-specific effects of the vaccine and its possible use as an inducer of trained immunity in vivo.