serovars Typhimurium and Enteritidis are the predominant causes of invasive non-typhoidal
(iNTS) disease. Considering the co-endemicity of
. Typhimurium and
. Enteritidis, a bivalent vaccine ...formulation against both pathogens is necessary for protection against iNTS disease, thus investigation of glycoconjugate combination is required. In the present work, we investigated the immune responses induced by
. Typhimurium and
. Enteritidis monovalent and bivalent glycoconjugate vaccines adjuvanted with aluminum hydroxide (alum) only or in combination with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG). Humoral and cellular, systemic and local, immune responses were characterized in two different mouse strains. All conjugate vaccines elicited high levels of serum IgG against the respective O-antigens (OAg) with bactericidal activity. The bivalent conjugate vaccine induced systemic production of antibodies against both
. Typhimurium and
. Enteritidis OAg. The presence of alum or alum + CpG adjuvants in vaccine formulations significantly increased the serum antigen-specific antibody production. The alum + CpG bivalent vaccine formulation triggered the highest systemic anti-OAg antibodies and also a significant increase of anti-OAg IgG in intestinal washes and fecal samples, with a positive correlation with serum levels. These data demonstrate the ability of monovalent and bivalent conjugate vaccines against
. Typhimurium and
. Enteritidis to induce systemic and local immune responses in different mouse strains, and highlight the suitability of a bivalent glycoconjugate formulation, especially when adjuvanted with alum + CpG, as a promising candidate vaccine against iNTS disease.
Abstract Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM197 , composed of the polysaccharide ...antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM197 , is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM197 . The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM197 was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM197 and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM197 as a promising candidate vaccine against Salmonella Typhi.
Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is a life-threatening disease with high rates of mortality and neurological sequelae. Immune targeting ...of S. pneumoniae is essential for clearance of infection; however, within the brain, the induced inflammatory response contributes to pathogenesis. In this study we investigate the local inflammatory response and the role of IFN-γ in a murine model of pneumococcal meningitis induced by intracranial injection of type 4 S. pneumoniae. Lymphoid and myeloid cell populations involved in meningitis, as well as cytokine gene expression, were investigated after infection. Animals were treated with a monoclonal antibody specific for murine IFN-γ to evaluate its role in animal survival. Intracranial inoculation of 3 × 10(4) colony-forming units of type 4 strain TIGR4 caused 75% of mice to develop meningitis within 4 days. The amount of lymphocytes, NK cells, neutrophils, monocytes and macrophages in the brain increased 48 h post infection. IFN-γ mRNA levels were about 240-fold higher in brains of infected mice compared to controls. Pro-inflammatory cytokines such as IL-1β and TNF-α, and TLR2 were also upregulated. In vivo treatment with anti-IFN-γ antibody increased survival of infected mice. This study shows that IFN-γ produced during meningitis by type 4 S. pneumoniae enhances bacterial pathogenesis exerting a negative effect on the disease outcome.
Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM197, composed of the polysaccharide antigen Vi ...covalently conjugated to the non-toxic mutant of diphtheria toxin CRM197, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM197. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM197was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM197and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM197as a promising candidate vaccine againstSalmonellaTyphi.
Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG ...oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A group of normal women of reproductive age were recruited to investigate colour discrimination during the various phases of the menstrual cycle. Colour vision was tested with the Farnsworth-Munsell ...100-hue arrangement test, and the test was administered at 3 time points: the beginning of the cycle, ovulation, and the end of the cycle. We found that colour discrimination was better at ovulation than at the other 2 time points. It is possible that psychological as well as hormonal factors could contribute to improved colour vision performance at ovulation.
AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus(HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic ...review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis(PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews:(1) HCV and haematopoietic malignancies;(2) HCV and cholangiocarcinoma;(3) HCV and pancreatic cancer;(4) HCV and breast cancer;(5) HCV and kidney cancer;(6) HCV and skin or oral cancer; and(7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with:(1) a higher incidence of some B-cell Non-HodgkinLymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%;(2) an increased risk of intra-hepatic cholangiocarcinoma; and(3) a correlation between HCV prevalence and pancreatic cancer(PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are requiredto confirm or deny this association.
MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis b- and c-related-hepatocellularcarcinoma Sirio Fiorino Maria Letizia Bacchi-Reggiani Michela Visani Giorgia Acquaviva Adele Fornelli Michele Masetti Andrea Tura Fabio Grizzi Matteo Zanello Laura Mastrangelo Raffaele Lombardi Luca Di Tommaso Arrigo Bondi Sergio Sabbatani Andrea Domanico Carlo Fabbri Paolo Leandri Annalisa Pession Elio Jovine Dario de Biase
世界胃肠病学杂志：英文版,
04/2016
15
Journal Article
Aim of the present review is to summarize the current knowledge about the potential relationship between mi RNAs and hepatitis B virus(HBV)-hepatitis C virus(HCV) related liver diseases. A systematic ...computerbased search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine mi RNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma(HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "micro RNAs", "mi RNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma mi RNAs, including mi R-21, mi R-122, mi-125a/b, mi R-199a/b, mi R-221, mi R-222, mi R-223, mi R-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of mi RNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of mi RNAs for HCC early detection and prognosis.
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