Synthetic self-adjuvanted lipopeptide vaccines conferred protection against Helicobacter pylori infection
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ABSTRACT:
PROVIDER: PRJNA938108 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22359677_1.fastq.gz | Fastqsanger.gz | |||
| SRR22359677_2.fastq.gz | Fastqsanger.gz | |||
| SRR22359678_1.fastq.gz | Fastqsanger.gz | |||
| SRR22359678_2.fastq.gz | Fastqsanger.gz | |||
| SRR22359679_1.fastq.gz | Fastqsanger.gz |
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Project description:Helicobacter pylori (H. pylori) colonize the stomach epithelium of half the world's population and are responsible for a variety of digestive diseases and even stomach cancer. The protection against H. pylori infection depends primarily on the antigen-mediated mucosal and T cell responses. We hypothesized that lipopeptide vaccines obtained by covalently conjugation of Pam2Cys with strong mucosal adjuvant activity to the immunodominant epitope from protective antigens could induce protective responses against H. pylori infection. In this study, the synthetic lipopeptide vaccines, Hp4 (Pam2Cys modified UreB T cell epitope) and Hp10 (Pam2Cys modified CagA T/B cell combined epitope), induced the BMDCs maturation in vitro by activating a variety of pattern recognition receptors such as TLR, NLR and RLR. In addition, lipopeptide vaccines stimulated BMDCs to secret cytokines that have the potential to modulate T cell activation and differentiation. Although intranasal immunization with Hp4 or Hp10 elicited robust epitope-specific T cell responses in mice, only Hp10 conferred protection against H. pylori infection, possibly due to the fact that Hp10 also induced substantial specific sIgA response at mucosal sites. Interestingly, when two lipopeptide vaccines were administrated in combination, Hp4 elevated the protective response against H. pylori infection of Hp10, which was characterized by better protective effect and enhanced specific T cell and mucosal antibody responses. Our results suggest that synthetic lipopeptide vaccines based on the epitopes derived from the protective antigens are promising candidates for protection against H. pylori infection.
2023-01-01 | GSE218459 | GEO
Project description:The continuing emergence of immune evasive SARS-CoV-2 variants and the previous SARS-CoV-1 outbreak have accentuated the need for broadly protective sarbecovirus vaccines. Targeting the conserved S2-subunit of SARS-CoV-2 is a particularly promising approach to elicit broad protection. Here, expanding on our previous work with S2-based vaccines, we developed a nanoparticle vaccine displaying multiple copies of the SARS-CoV-1 S2 subunit. This vaccine alone, or as a cocktail with a SARS-CoV-2 S2 subunit vaccine, protected female transgenic K18-hACE2 mice from challenges with Omicron subvariant XBB as well as several sarbecoviruses identified as having pandemic potential including the bat sarbecovirus WIV1, BANAL-236, and a pangolin sarbecovirus. Challenge studies in female Fc- receptor knockout mice revealed that antibody-based cellular effector mechanisms played a role in protection elicited by these vaccines. These results demonstrate that our S2-based vaccines provide broad protection against clade 1 sarbecoviruses and offer insight into the mechanistic basis for protection.
2024-11-21 | GSE282247 | GEO
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| S-EPMC4981723 | biostudies-literature
Project description:Two decades after the introduction of oil-based vaccines in the control of bacterial and viral diseases in farmed salmonids, the mechanisms of induced side effects manifested as intra-abdominal granulomas remain unresolved. Side effects have been associated with generation of auto-antibodies and autoimmunity but underlying profile of the inflammatory and immune response has not been characterized. This study was undertaken with the aim to elucidate the inflammatory and immune mechanisms of granuloma formation at gene expression level associated with high and low side effect (granuloma) indices. Groups of Atlantic salmon parr were injected intraperitoneally with oil-adjuvanted vaccines containing either high or low concentrations of Aeromonas salmonicida or Moritella viscose antigens in order to induce polarized (severe and mild) granulomatous reactions. The established granulomatous reactions were confirmed by gross and histological methods at 3 months post vaccination when responses were known to have matured. The corresponding gene expression patterns in the head kidneys were profiled using salmonid cDNA microarrays followed by validation by real-time quantitative PCR (qPCR). qPCR was also used to examine the expression of additional genes known to be important in the adaptive immune response. Granulomatous lesions were observed in all vaccinated fish. Presence of severe granulomas were associated with a profile of up-regulation of innate immunity-related genes such as complement factors C1q and C6, mannose binding protein, lysozyme C, C-type lectin receptor, CD209, Cathepsin D, CD63, LECT-2, CC chemokine and metallothionein. In addition, IL-17A (Th17) was significantly up-regulated (p=0.009) in the group with severe granulomas as were arginase and IgM. None of the genes directly reflective of Th1 T cell lineage (IFN-γ, CD4) or Th2 (GATA-3) differentiation were differentially expressed. Granulomatous reactions following vaccination with oil-based vaccines in Atlantic salmon has the profile of strong expression of genes related to innate immune responses. The expression of IL-17A suggests an involvement of Th17 T cell lineage and is in conformity with strong infiltration of neutrophils and macrophages into inflamed areas. Arginase upregulation shows that macrophages in these reactions are alternatively activated, indicating a Th2-bias. To what extent the IL-17A profile reflects an autoimmune vaccine-based reaction remains elusive but would be in conformity with previous observations of autoimmune reactions in salmon vaccinated with oil-based vaccines. RNA from 12 head kidney samples (12 fish) per group were pooled into groups of 4. The RNA was amplified prior to hybridization to arrays. Three biological and 2 technical replicates (dye-swapped) were utilized in different combinations to hybridize to 18 arrays using RNA from fish with the least injection-site inflammatory reactions (FO-1) as the reference group. The assignment of microarrays to treatment groups for hybridization was randomised by using a random number generator. To minimize technical variability, target synthesis was done in batches of 6 where all treatment groups were equally represented.
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Project description:The immune response against tuberculosis relies, at least in part, on CD4+ T cells. Protective vaccines require the induction of antigen-specific CD4+ T cells via mycobacterial peptides presented by MHC class-II in infected macrophages. We have purified MHC class-I and MHC-II peptides and analysed them by mass spectrometry. We have successfully identified 97 mycobacterial peptides presented by MHC-II and 54 presented by MHC-I, from 76 and 41 antigens, respectively. The sequences of selected peptides were confirmed by spectral match validation and immunogenicity evaluated by IFN-gamma ELISpot against peripheral blood mononuclear cells from volunteers vaccinated with BCG, M.tb latently infected subjects or patients with tuberculosis disease. Three antigens were expressed in viral vectors, and evaluated as vaccine candidates alone or in combination in a murine aerosol M.tb challenge model. When delivered in combination, the three candidate vaccines conferred significant protection in the lungs and spleen compared with BCG alone, demonstrating proof-of-concept for this unbiased approach to identifying novel candidate antigens.
2020-01-08 | E-MTAB-8057 | biostudies-arrayexpress
Project description:Human dendritic cells play a fundamental role in the initiation of long-term adaptive immunity during vaccination against influenza. Understanding the early response of human DCs to vaccine challenge is thus essential to determine the nature and magnitude of maturation signals that strongly correlate with vaccine effectiveness. Here, we show that the non-adjuvanted trivalent Fluzone®09-10 (TIV-09) induces monocyte-derived DCs (moDCs), purified blood conventional DCs (cDCs) and plasmacytoid DCs (pDCs) to express CD80, CD83, and CD86, and secrete cytokines. TIV-09 stimulated the secretion of type I interferons (IFN) IFN-α and IFN-β and type III IFN IL-29 by moDCs and cDCs subsets. The vaccine also induced the production of IL-6, TNF and the chemokines IP-10 and MIP-1β. Conversely, the non-adjuvanted monovalent H1N1 California vaccine (MIV-09), which was commercialized in 2009 during the H1N1 epidemics and displayed lower effectiveness in retrospective studies, did not induce the production of type I IFN in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFN by these DCs. Yet, both vaccines induced pDCs to secrete type I IFN indicating that different influenza vaccines activate different molecular signaling pathways in different DC subsets. In vivo, the baseline IFN signature was decreased upon administration of the H1N1 vaccine in 3/3 pediatric lupus patients. These results suggest that subtypes of non-adjuvanted influenza vaccines elicit long-term protection through different mechanisms and that a vaccine’s ability to induce an IFN response in DCs may palliate the absence of adjuvant and increase vaccine efficacy.
2016-12-25 | GSE81691 | GEO
Project description:Human dendritic cells play a fundamental role in the initiation of long-term adaptive immunity during vaccination against influenza. Understanding the early response of human DCs to vaccine challenge is thus essential to determine the nature and magnitude of maturation signals that strongly correlate with vaccine effectiveness. Here, we show that the non-adjuvanted trivalent Fluzone®09-10 (TIV-09) induces monocyte-derived DCs (moDCs), purified blood conventional DCs (cDCs) and plasmacytoid DCs (pDCs) to express CD80, CD83, and CD86, and secrete cytokines. TIV-09 stimulated the secretion of type I interferons (IFN) IFN-α and IFN-β and type III IFN IL-29 by moDCs and cDCs subsets. The vaccine also induced the production of IL-6, TNF and the chemokines IP-10 and MIP-1β. Conversely, the non-adjuvanted monovalent H1N1 California vaccine (MIV-09), which was commercialized in 2009 during the H1N1 epidemics and displayed lower effectiveness in retrospective studies, did not induce the production of type I IFN in moDCs and blood cDCs. Furthermore, it inhibited the TIV-09-induced secretion of type I IFN by these DCs. Yet, both vaccines induced pDCs to secrete type I IFN indicating that different influenza vaccines activate different molecular signaling pathways in different DC subsets. In vivo, the baseline IFN signature was decreased upon administration of the H1N1 vaccine in 3/3 pediatric lupus patients. These results suggest that subtypes of non-adjuvanted influenza vaccines elicit long-term protection through different mechanisms and that a vaccine’s ability to induce an IFN response in DCs may palliate the absence of adjuvant and increase vaccine efficacy.
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2022-02-20 | GSE196938 | GEO
Project description:Yersinia pestis, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate potential gene expression markers that correlated with macrophage protection. Here, we report for the first time in humans that inverse caspase 3 levels which are measures of protective antibody significantly increased by 29% and 75% on day 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4+ T cell responses. Several genes associated with macrophage-protective antibody were identified that could serve as potential correlates of protection.
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