1,354,179 research outputs found
Bacillus spores for vaccine delivery
No full textSpores of the genus Bacillus have been used for a long time as probiotics for oral bacteriotherapy both in humans and in animals. Spores are also employed in a veterinary vaccine against anthrax. Despite this long lasting and extensive use, the specific contribution of spores to the beneficial effects of probiotics and to the immunogenicity of the vaccine is not completely elucidated. This review focuses on the different aspects of the use of spore preparations. In particular the use of recombinant spores as vaccine delivery vehicles is described and discussed
Profiling the B cell immune response elicited by vaccination against the respiratory virus SARS-CoV-2
No full textB cells play a fundamental role in host defenses against viral infections. Profiling the B cell response elicited by SARS-CoV-2 vaccination, including the generation and persistence of antigen-specific memory B cells, is essential for improving the knowledge of vaccine immune responsiveness, beyond the antibody response. mRNA-based vaccines have shown to induce a robust class-switched memory B cell response that persists overtime and is boosted by further vaccine administration, suggesting that memory B cells are critical in driving a recall response upon re-exposure to SARS-CoV-2 antigens. Here, we focus on the role of the B cell response in the context of SARS-CoV-2 vaccination, offering an overview of the different technologies that can be used to identify spike-specific B cells, characterize their phenotype using machine learning approaches, measure their capacity to reactivate following antigen encounter, and tracking the maturation of the B cell receptor antigenic affinity
From bivariate to multivariate analysis of cytometric data: overview of computational methods and their application in vaccination studies
No full textFlow and mass cytometry are used to quantify the expression of multiple extracellular or intracellular molecules on single cells, allowing the phenotypic and functional characterization of complex cell populations. Multiparametric flow cytometry is particularly suitable for deep analysis of immune responses after vaccination, as it allows to measure the frequency, the phenotype, and the functional features of antigen-specific cells. When many parameters are investigated simultaneously, it is not feasible to analyze all the possible bi-dimensional combinations of marker expression with classical manual analysis and the adoption of advanced automated tools to process and analyze high-dimensional data sets becomes necessary. In recent years, the development of many tools for the automated analysis of multiparametric cytometry data has been reported, with an increasing record of publications starting from 2014. However, the use of these tools has been preferentially restricted to bioinformaticians, while few of them are routinely employed by the biomedical community. Filling the gap between algorithms developers and final users is fundamental for exploiting the advantages of computational tools in the analysis of cytometry data. The potentialities of automated analyses range from the improvement of the data quality in the pre-processing steps up to the unbiased, data-driven examination of complex datasets using a variety of algorithms based on different approaches. In this review, an overview of the automated analysis pipeline is provided, spanning from the pre-processing phase to the automated population analysis. Analysis based on computational tools might overcame both the subjectivity of manual gating and the operator-biased exploration of expected populations. Examples of applications of automated tools that have successfully improved the characterization of different cell populations in vaccination studies are also presented
CD4+ T-cell priming as biomarker to study immune response to preventive vaccines
No full textT-cell priming is a critical event in the initiation of the immune response to vaccination since it deeply influences both the magnitude and the quality of the immune response induced. CD4+ T-cell priming, required for the induction of high-affinity antibodies and immune memory, represents a key target for improving and modulating vaccine immunogenicity. A major challenge in the study of in vivo T-cell priming is due to the low frequency of antigen-specific T cells. This review discusses the current knowledge on antigen-specific CD4+ T-cell priming in the context of vaccination, as well as the most advanced tools for the characterization of the in vivo T-cell priming and the opportunities offered by the application of systems biology
Adoptive transfer of transgenic T cells to study mucosal adjuvants
No full textThe study of the initiation and regulation of T-cell responses to vaccine antigens is of primary importance in the rational design of mucosal adjuvants. The detection in vivo of T-cell priming following immunization can be performed by using the adoptive transfer model of naïve antigen-specific transgenic T cells into immunocompetent mice. In this work, we discuss the applications of this system for detecting in vivo the primary antigen-specific clonal expansion, the phenotype, and the effector function of transgenic T cells following mucosal immunization. OVA and the mucosal adjuvant CTB were used as a model vaccine formulation and administered by the nasal route to study T-cell priming. T helper and T cytotoxic primary proliferation and expression of activation and migration markers was observed both in draining and distal sites. This method proved to be a powerful tool to study the efficacy of mucosal adjuvants in enhancing T-cell priming
Primary activation of antigen-specific naive CD4+ and CD8+ T cells following intranasal vaccination with recombinant bacteria
No full textThe primary activation of T-helper and T-cytotoxic cells following mucosal immunization with recombinant Streptococcus gordonii was studied in vivo by adoptive transfer of ovalbumin (OVA)-specific transgenic CD8(+) (OT-I) and CD4(+) (OT-II) T cells. A recombinant strain, expressing on the surface the vaccine antigen Ag85B-ESAT-6 from Mycobacterium tuberculosis fused to OVA T-helper and T-cytotoxic epitopes (peptides 323 to 339 and 257 to 264), was constructed and used to immunize C57BL/6 mice by the intranasal route. Recombinant, but not wild-type, bacteria induced OVA-specific CD4(+) and CD8(+) T-cell clonal expansion in cervical lymph nodes, lung, and spleen. OVA-specific CD4(+) and CD8(+) T-cell proliferation appeared first in cervical lymph nodes and later in the spleen, suggesting a possible migration of activated cells from the inductive site to the systemic district. A significant correlation between the percentages of CD4(+) and CD8(+) proliferating T cells was observed for each animal. The expression of CD69, CD44, and CD45RB on proliferating T lymphocytes changed as a function of the cell division number, confirming T-cell activation following the antigen encounter. These data indicate that intranasal immunization with recombinant S. gordonii is capable of inducing primary activation of naive antigen-specific CD4(+) and CD8(+) T cells, both locally and systemically
Role of the microbiota in the modulation of vaccine immune responses
No full textThe human immune system and the microbiota co-evolve, and their balanced relationship is based on crosstalk between the two systems through the course of life. This tight association and the overall composition and richness of the microbiota play an important role in the modulation of host immunity and may impact the immune response to vaccination. The availability of innovative technologies, such as next-generation sequencing (NGS) and correlated bioinformatics tools, allows a deeper investigation of the crosstalk between the microbiota and human immune responses. This review discusses the current knowledge on the influence of the microbiota on the immune response to vaccination and novel tools to deeply analyze the impact of the microbiome on vaccine responses
Intranasal immunization with vaccine vector Streptococcus gordonii elicits primed CD4(+) and CD8(+) T cells in the genital and intestinal tracts
No full textGeneration of primed T cells is crucial for the development of optimal vaccination strategies. Using a TCR-transgenic CD4(+) and CD8(+) T cell adoptive transfer model, we demonstrate that a single nasal immunization with recombinant Streptococcus gordonii induces antigen-specific primed T cells in lymph nodes draining the genital and intestinal tracts with about 80% of CD4(+) and 50% of CD8(+) proliferating cells. T cell clonal expansion was also observed in cervical lymph nodes, draining the immunization site, and in the spleen. The modulation of CD44 and CD45RB marker expression indicated that proliferating T cells were activated. Proliferation in distal mesenteric and iliac lymph nodes and in the spleen was observed 5 days after nasal immunization, while in draining cervical lymph nodes proliferation peaked already at day 3. The division profile of transgenic T cells observed in iliac and mesenteric lymph nodes was discontinuous, showing the lack of early cell divisions. The kinetics of T cell clonal expansion, the discontinuous division profile and the modulation of migration markers such as CD62L suggest that activated antigen-specific T cells disseminate from the immunization site to distal intestinal and genital tracts. These data demonstrate the efficacy of nasal immunization with recombinant S. gordonii in eliciting CD4(+) and CD8(+) T cell priming not only in draining sites, but also in the genital and intestinal tracts and in the spleen
Oral priming of mice by recombinant spores of Bacillus subtilis
No full textRecombinant Bacillus subtilis spores were employed as a vaccine delivery system in a heterologous mucosal priming-parenteral boosting vaccination strategy in the mouse model. BALB/c and C57BL/6 mice were orally immunised with recombinant spores expressing tetanus toxin fragment C (TTFC) fused to the spore outer coat protein CotB, and then subcutaneously boosted with soluble TTFC (without adjuvant). Two weeks after boosting, a significantly higher serum TTFC-specific IgG response was stimulated in mice primed with recombinant spores (antibody concentration of 2600 +/- 915 in C57BL/6 and 1200 +/- 370 ng/ml in BALB/c) compared to mice inoculated with wild type spores (650 +/- 250 and 250 +/- 130 ng/ml, respectively). IgG subclass analysis showed a prevalence of IgG1 and IgG2b, indicative of a Th2 type of immune response. Oral administration of recombinant spores stimulated also a significant local TTFC-specific IgA response. These data show that recombinant spores of B. subtilis are able to prime the immune system by the oral route, and that a combined mucosal/parenteral strategy can stimulate both local and systemic antigen-specific immune responses
Are Local Group Dwarf Spheroidal Galaxies the First Safe Planet-hosting Environments?
No full textWe explore whether Local Group dwarf spheroidal (dSph) galaxies might have hosted Earth-like planets dwelling unexposed for several billions of years to major galactic threats to life, such as supernovae and gamma-ray bursts. To this aim, we developed a novel semiempirical model that exploits the observed chemical abundances and star formation histories of a selected sample of local dSphs, to explore whether their stars may have (i) reached the minimum metallicity to trigger planet formation and (ii) avoided exposure to destructive events long enough to provide time for possible biological development. From our work two scenarios emerge. If planet formation is possible for [Fe/H] ≲ −1, then in all dSphs with 5 × 103 L⊙ ≤ LV ≤ 2 × 107 L⊙ a fraction ≈0.1%-10% of stars might have safely hosted terrestrial planets for more than 1 Gyr. In this scenario, ancient ultrafaint dwarf galaxies (UFDs, LV ≤ 105 L⊙) would have been the first to reach this condition in the history of the Local Group. Conversely, if planets form for [Fe/H] ≥ −0.6 then they should not exist in UFDs, while only ≈0.001%-0.1% of stars in dSphs with LV ≥ 3 × 105 L⊙ would host planets dwelling in safe conditions for long times. Interestingly, we find a “luminosity sweet spot” at LV ∼ 106 L⊙, where dSphs in our sample safely host terrestrial planets up to 4 Gyr and in any planet formation scenario explored. In conclusion, planet formation at low metallicity is key to understanding which types of galaxies might have formed Earth-like planets that dwelt unexposed to galactic threats over several billions of years, first in the history of the Local Group
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