1,721,056 research outputs found
Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine
Full text linkThe rVSV-ZEBOV vaccine is currently the only Ebola vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature. © 2017 The Author
The role of the vaccines industry in Mission Grand Convergence
No full textThe vast majority of vaccines used throughout the world are supplied by the private sector. It is essential therefore that the industry is closely engaged in future policy developments at a national and international level and is able to respond to the changing needs and priorities that may be required to ensure the success of Mission Grand Convergence. Uniquely, the major vaccine companies have the expertise and technical capacity to develop, produce and supply vaccines on a global scale. Through partnering with Governments, charities and NGOs, they must play a pivotal role in the Mission and, at the same time as agreeing on objectives that may not be entirely market driven, must be able to sustain their commercial obligations to shareholders. Similarly, small and medium sized companies, with the global investor market and government incentives that underpin and support them, also have a very important role to play; for example in innovation around a given disease and on technology, process and platform development across the whole value chain. The industry at large is therefore an essential player. Indeed Mission Grand Convergence can only succeed with the full and willing participation of the vaccines industry. © 2016 Elsevier Lt
Mucosal adjuvants
No full textThe vast majority of pathogens invade the body through or establish infections in the mucosal tissues. Development of vaccines to combat mucosal infections represents a top priority. Mucosal immunization has recently attracted much interest as a means of generating protective immunity against mucosal pathogens. Conversely, only very few mucosal vaccines are presently approved for human use. The development of a broad range of mucosal vaccines will necessitate the development of safe and effective mucosal adjuvants and delivery systems. Over the past decade, a number of immunomodulatory agents, including toxin based adjuvants, Toll like receptor (TLR) mimetics and non TLR-targeting immunostimulators as well as delivery systems have shown promise for mucosal administration in experimental animals. However, their possible use in humans remains to be established. This paper attempts to provide a brief overview of the mucosal immunization and adjuvants with an emphasis on mucosal adjuvants in or close to clinic
Vaginal immunization with recombinant gram-positive bacteria
No full textPROBLEM:
Many viral and bacterial pathogens enter the body through the genital mucosa. Therefore, one of the major goals of a vaccine against sexually transmitted diseases (STDs) should be to induce an immune response in the genital mucosa capable of controlling the entry of the pathogen. Our approach for the development of vaccines against STDs is based on the use of nonpathogenic Gram-positive bacteria as live vaccine vectors.
METHOD OF STUDY:
Recombinant Gram-positive bacteria expressing vaccine antigens were constructed using genetic systems developed in our laboratory. Balb/c mice and Cynomolgus monkeys were inoculated by the vaginal route and vaginal samples were collected using absorbent wicks. Colonization was evaluated by the presence of recombinant bacteria in the vaginal samples. Local and systemic immune responses were studied.
RESULTS:
We have developed genetic systems for the expression of heterologous antigens on the surface of the human commensals Streptococcus gordonii and Lactobacillus spp. Both S. gordonii and L. casei stably colonized the murine vagina after a single inoculum. Vaginal colonization of mice with recombinant strains of S. gordonii, expressing human papillomavirus (HPV) and human immunodeficiency virus (HIV) antigens, induced antigen-specific vaginal immunoglobulin A (IgA) and serum IgG. Local and systemic immune responses also were detected in monkeys immunized intravaginally with recombinant S. gordonii.
CONCLUSION:
The results obtained indicated that the approach of using colonizing Gram-positive bacteria as live vectors has a great potential for the development of vaccines against STDs
From bivariate to multivariate analysis of cytometric data: overview of computational methods and their application in vaccination studies
Full text linkFlow 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
Recombinant Streptococcus gordonii as live vehicle for vaccine antigens
No full textAll recombinant strains, including the parent recombinant S. gordonii GP231 expressing whole M6, do produce in liquid culture the cloned proteins from mid mid exponential phase of growth to the late stationary phase. The maximum protein quantity per cell is detected about one generation after the beginning of the stationary phase (Medaglini et al., 1993). This characteristic enables to collect the bacterial cells for protein analysis and purification purposes at the highest possible cell density. Recombinant proteins are detected in media containing no dextrose (Tryptic Soy Broth without dextrose) and in standard media containing 0.2% of glucose, while the protein quantity diminishes, in stationary phase of growth, when high glucose containing media (1, 2, 5 10% glucose) are used possibly due to proteolytic degradation. On solid media the recombinant proteins are produced and are detectable since the colony becomes visible on the plate and thus making protein detection through colony blot screening possible. Cell fractioning, immunofluorescence and electron microscopy on bacteria grown to late exponential phase did confirm surface display of the M6-based fusion proteins
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
Full text linkThe 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
Engineering the gram-positive cell surface for construction of bacterial vaccine vectors
No full textA genetic system for surface display of heterologous proteins has been developed in Streptococcus gordonii, a gram-positive human oral commensal that is naturally competent for genetic transformation. Our approach is based on chromosomal integration downstream from a resident promoter and translational fusion to an M6 protein. Using this strategy a variety of proteins, of different origin and size, were displayed on the cell surface and were shown to be stably expressed both in vitro and in vivo. Animal models of mucosal colonization (oral and vaginal) and intragastric immunization with recombinant S. gordonii were developed and the local and systemic immune responses were studied. Here we report the techniques for the construction of recombinant bacteria, use of animal models, and analysis of the immune response
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