Vaccines combining slow release and follicle targeting of antigens increase germinal center B cell clonal diversity and clonal expansion
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PROVIDER: PRJNA1217578 | ENA |
REPOSITORIES: ENA
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Project description:Vaccines incorporating slow release, multivalent antigen display, and/or immunomodulation through adjuvants have important roles in shaping the humoral immune response. Here, we analyzed mechanisms of action of a clinically relevant combination adjuvant strategy, where phosphoserine (pSer)-tagged immunogens bound to aluminum hydroxide (alum) adjuvant (promoting prolonged antigen release to draining lymph nodes) are combined with a potent saponin nanoparticle adjuvant termed SMNP (which alters lymph flow and antigen entry into lymph nodes). When employed with a stabilized HIV Env trimer antigen in mice, this combined adjuvant approach promoted substantial enhancements in germinal center (GC) and antibody responses relative to either adjuvant alone. Using scRNA-seq and scBCR-seq, we found that the alum-pSer/SMNP combination augmented the clonal expansion and diversity of GC B cell repertoire, coincident with increased expression of positive selection markers and proportion of S-phase GC B cells. To gain insight into the source of these changes in the GC response, we analyzed antigen biodistribution and structural integrity in draining lymph nodes and found that the combination adjuvant approach, but not alum-pSer delivery or SMNP alone, promoted accumulation of intact antigen on follicular dendritic cells (FDCs), reflecting an integration of the effects by slowing antigen release and altering lymph node uptake. Ablating the Cr1/2 complex on FDCs significantly hampered antigen-specific GC response, corroborating enhanced FDC decoration as the key mechanism of improved vaccine response. These results demonstrate how adjuvants with complementary mechanisms of action impacting vaccine biodistribution and kinetics can synergize to enhance humoral immunity.
2025-02-04 | GSE288450 | GEO
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:Identification of antigens presented by MHC for vaccines against tuberculosis
| PRJEB33057 | ENA
Project description:Vaccines to prevent capsular group B meningococcal disease have been based on proteins, as the polysaccharide capsule was deemed unsuitable due to its similarity to human tissues. Outer membrane vesicle (OMV) vaccines have been targeted at specific capsular group B epidemics in Cuba, Norway, and New Zealand, with the major immunogen determined as porin A (PorA). Subcapsular protein vaccines aim to increase breadth of coverage of meningococcal strains, by the inclusion of protein variants from many different clonal complexes (ccs). Using scalable and portable genomic techniques, it is possible to study the diversity of OMV and subcapsular proteins in relevant meningococcal populations. Shotgun proteomics identified 461 proteins in the OMVs derived from NZ98/254, a component of the Bexsero® vaccine, with a complex proteome comprised of outer membrane proteins and proteins from other cellular compartments. Amino acid sequences for 24 selected proteins were catalogued within the PubMLST Neisseria database as part of the OMV peptide Typing (OMVT) scheme. Of the 24 proteins included, there was variation in the extent of diversity and association with ccs from the most conserved peptides FbpA (NEISp0578) and putative periplasmic proteins (NEISp1063) to the most diverse TbpA (NEISp1690). There were 1752 OMVTs identified amongst 2492/3506 isolates. OMVTs were further grouped into clusters (identical at ≥18 peptide sequences), 45.3% of isolates were assigned to one of 27 OMVT clusters. Both OMVTs and clusters were strongly associated with cc, genogroup and recombinant Bexsero® antigens. The OMVT scheme represents an open-access, web-based tool for the systematic analysis of the multiple components of OMV vaccines, demonstrating that combinations of OMV proteins exist in discrete, non-overlapping combinations associated with both genogroup and Bexsero® Antigen Sequence type (BAST). This highly structured population of disease-causing meningococci is consistent with proposed effects of host immune selection and competition between allelic variants on meningococcal population structure. This has implications for future vaccine assessment, and development, especially the choice of antigen combinations. The methodology is portable and will facilitate region-specific WGS interrogation, allowing informed choices about vaccine development or implementation.
2018-11-14 | PXD011622 | Pride
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.
2019-05-14 | PXD013804 | Pride
Project description:Transcriptome analysis of total blood cells from sheep collected at 0, 4 and 24 hours after vaccination with inactivated FMDV vaccine, and adenovirus (human Ad5)-based vaccines encoding FMDV antigens, with and without Montanide ISA206 VG adjuvant.
2019-12-10 | GSE135609 | GEO
Project description:Purpose: This study uses a high-throughput glycan microarray to profile anti-glycan immune responses to whole-cell vaccines: GVAX Pancreas, K562-GM and H1299. The aim was to indentify anti-glycan antibody responses relevent to patient clinical outcomes Results: Immune responses to non-human antigens bovine fetuin and alpha-Gal antigens were identified induced by GVAX Pancreas. The magnitude of these responses inversely correlate with patient survival. The non-human antigens were likely incorporated from cell media used for vaccine production. Their presence distracted immune system, resulting in decreased immune response to vaccine antigens. Conclusion: This study highlighted the importance of anti-glycan immune response in vaccine development. Whole-cell vaccinesderived from human cell lines could incorporate non-human antigens from cell media. These xeno-antigens may have negative impact on the vaccine efficacy.
2016-12-13 | GSE83087 | GEO
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:Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic progressive granulomatous enteritis leading to diarrhea, weight loss, and eventual death in ruminants. Commercially available vaccines provide only partial protection against MAP infection and can interfere with the use of current diagnostic tests for bovine tuberculosis in cattle. In the current study, we characterized immune responses in calves to vaccines containing either MAP fusion protein particles (MAP antigens Ag85A202-347-SOD1-72 -Ag85B173-330-74F1-148+669-786 as a fusion), recombinant MAP (rMAP) fusion protein or commercially available Silirum(R) vaccine.
2022-12-21 | GSE221544 | GEO