237 research outputs found

    Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines - Exploratory Analyses within a Randomised Controlled Trial

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    Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.peer-reviewe

    Functionalising the azobenzene motif delivers a light-responsive membrane-interactive compound with the potential for photodynamic therapy applications

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    When adorned with n-octyl chains azobenzene is able to disrupt a variety of calcein-loaded phospholipid liposomes. The levels of lysis observed are dependent both on the lipid headgroup and the conformation of the azobenzene compound. In all cases studied, it has been shown that the cis-conformer is more membrane-interactive than the trans-conformer, suggesting that this class of molecule could be optimised for photo-dynamic therapy applications against infectious pathogens

    Antibody persistence and booster responses to split-virion H5N1 avian influenza vaccine in young and elderly adults

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    Avian influenza continues to circulate and remains a global health threat not least because of the associated high mortality. In this study antibody persistence, booster vaccine response and cross-clade immune response between two influenza A(H5N1) vaccines were compared. Participants aged over 18-years who had previously been immunized with a clade 1, A/Vietnam vaccine were re-immunized at 6-months with 7.5 mu g of the homologous strain or at 22-months with a clade 2, alum-adjuvanted, A/Indonesia vaccine. Blood sampled at 6, 15 and 22-months after the primary course was used to assess antibody persistence. Antibody concentrations 6-months after primary immunisation with either A/Vietnam vaccine 30 mu g alum-adjuvanted vaccine or 7.5 mu g dose vaccine were lower than 21days after the primary course and waned further with time. Re-immunization with the clade 2, 30 mu g alum-adjuvanted vaccine confirmed cross-clade reactogenicity. Antibody crossreactivity between A(H5N1) clades suggests that in principle a prime-boost vaccination strategy may provide both early protection at the start of a pandemic and improved antibody responses to specific vaccination once available

    Attitudes of pregnant women and healthcare professionals towards clinical trials and routine implementation of antenatal vaccination against respiratory syncytial virus : a multicenter questionnaire study

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    Introduction: Respiratory syncytial virus (RSV) is a common cause of infant hospitalization and mortality. With multiple vaccines in development, we aimed to determine: (1) the awareness of RSV among pregnant women and healthcare professionals (HCPs), and (2) attitudes toward clinical trials and routine implementation of antenatal RSV vaccination.Methods: Separate questionnaires for pregnant women and HCPs were distributed within 4 hospitals in South England (July 2017–January 2018).Results: Responses from 314 pregnant women and 204 HCPs (18% obstetricians, 75% midwives, 7% unknown) were analyzed. Most pregnant women (88%) and midwives (66%) had no/very little awareness of RSV, unlike obstetricians (14%). Among pregnant women, 29% and 75% would likely accept RSV vaccination as part of a trial, or if routinely recommended, respectively. Younger women (16–24 years), those of 21–30 weeks’ gestation, and with experience of RSV were significantly more likely to participate in trials [odds ratio (OR): 1.42 (1.72–9.86); OR: 2.29 (1.22–4.31); OR: 9.07 (1.62–50.86), respectively]. White-British women and those of 21–30 weeks’ gestation were more likely to accept routinely recommended vaccination [OR: 2.16 (1.07–4.13); OR: 2.10 (1.07–4.13)]. Obstetricians were more likely than midwives to support clinical trials [92% vs. 68%, OR: 2.50 (1.01–6.16)] and routine RSV vaccination [89% vs. 79%, OR: 4.08 (1.53–9.81)], as were those with prior knowledge of RSV, and who deemed it serious.Conclusions: RSV awareness is low among pregnant women and midwives. Education will be required to support successful implementation of routine antenatal vaccination. Research is needed to understand reasons for vaccine hesitancy among pregnant women and HCPs, particularly midwives.<br/

    Ni Mg mixed metal oxides for p-type dye-sensitized solar cells

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    Mg Ni mixed metal oxide photocathodes have been prepared by a mixed NiCl2/MgCl2 sol-gel process. The MgO/NiO electrodes have been extensively characterized using physical and electrochemical methods. Dye-sensitized solar cells have been prepared from these films and the higher concentrations of MgO improved the photovoltage of these devices, however, there was a notable drop in photocurrent with increasing Mg2+. Charge extraction and XPS experiments revealed that the cause of this was a positive shift in the energy of the valence band which decreased the driving force for electron transfer from the NiO film to the dye and therefore the photocurrent. In addition, increasing concentrations of MgO increases the volume of pores between 0.500 to 0.050 μm, while reducing pore volumes in the mesopore range (less than 0.050 μm) and lowering BET surface area from approximately 41 down to 30 m2 g-1. A MgO concentration of 5% was found to strike a balance between the increased photovoltage and decreased photocurrent, possessing a BET surface area of 35 m2 g-1 and a large pore volume in both the meso and macropore range, which lead to a higher overall power conversion efficiency than NiO alone

    Ebola virus glycoprotein stimulates IL-18 dependent natural killer cell responses

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    BACKGROUNDNK cells are activated by innate cytokines and viral ligands to kill virus-infected cells. These functions are enhanced during secondary immune responses and after vaccination by synergy with effector T cells and virus-specific antibodies. In human Ebola virus infection, clinical outcome is strongly associated with the initial innate cytokine response, but the role of NK cells has not been thoroughly examined.METHODSThe novel 2-dose heterologous Adenovirus type 26.ZEBOV (Ad26.ZEBOV) and modified vaccinia Ankara-BN-Filo (MVA-BN-Filo) vaccine regimen is safe and provides specific immunity against Ebola glycoprotein, and is currently in phase 2 and 3 studies. Here, we analyzed NK cell phenotype and function in response to Ad26.ZEBOV, MVA-BN-Filo vaccination regimen and in response to in vitro Ebola glycoprotein stimulation of PBMCs isolated before and after vaccination.RESULTSWe show enhanced NK cell proliferation and activation after vaccination compared with baseline. Ebola glycoprotein-induced activation of NK cells was dependent on accessory cells and TLR-4-dependent innate cytokine secretion (predominantly from CD14+ monocytes) and enriched within less differentiated NK cell subsets. Optimal NK cell responses were dependent on IL-18 and IL-12, whereas IFN-γ secretion was restricted by high concentrations of IL-10.CONCLUSIONThis study demonstrates the induction of NK cell effector functions early after Ad26.ZEBOV, MVA-BN-Filo vaccination and provides a mechanism for the activation and regulation of NK cells by Ebola glycoprotein.TRIAL REGISTRATIONClinicalTrials.gov NCT02313077.FUNDINGUnited Kingdom Medical Research Council Studentship in Vaccine Research, Innovative Medicines Initiative 2 Joint Undertaking, EBOVAC (grant 115861) and Crucell Holland (now Janssen Vaccines and Prevention B.V.), European Union's Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA)

    Antibody-Dependent Natural Killer Cell Activation after Ebola Vaccination

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    BACKGROUND:Antibody Fc-mediated functions, such as antibody-dependent cellular cytotoxicity, contribute to vaccine-induced protection against viral infections. Fc-mediated function of anti-Ebola glycoprotein antibodies suggest that Fc-dependent activation of effector cells, including NK cells, could play a role in vaccination against Ebola virus disease. METHODS:We analysed the effect of anti-Ebola glycoprotein antibody in the serum of U.K.-based volunteers vaccinated with the novel 2-dose heterologous Adenovirus type 26.ZEBOV, Modified Vaccinia Ankara-BN-Filo vaccine regimen, on primary human NK cell activation. RESULTS:We demonstrate primary human NK cell CD107a and IFN-γ expression, combined with downregulation of CD16, in response to recombinant Ebola virus glycoprotein and post-vaccine dose 1 and dose 2 sera. These responses varied significantly with vaccine regimen and NK cell activation was found to correlate with anti-glycoprotein antibody concentration. We also reveal an impact of NK cell differentiation phenotype on antibody-dependent NK cell activation, with highly differentiated CD56dimCD57+ NK cells being the most responsive. CONCLUSIONS:This study thus highlights the dual importance of vaccine-induced antibody concentration and NK cell differentiation status in promoting Fc-mediated activation of NK cells after vaccination, raising a potential role for antibody-mediated NK cell activation in vaccine-induced immune responses

    Microplastic ingestion ubiquitous in marine turtles

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    Despite concerns regarding the environmental impacts of microplastics, knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we utilize an optimized enzymatic digestion methodology, previously developed for zooplankton, to explore whether synthetic particles could be isolated from marine turtle ingesta. We report the presence of synthetic particles in every turtle subjected to investigation (n = 102) which included individuals from all seven species of marine turtle, sampled from three ocean basins (Atlantic [ATL]: n = 30, four species; Mediterranean (MED): n = 56, two species; Pacific (PAC): n = 16, five species). Most particles (n = 811) were fibres (ATL: 77.1% MED: 85.3% PAC: 64.8%) with blue and black being the dominant colours. In lesser quantities were fragments (ATL: 22.9%: MED: 14.7% PAC: 20.2%) and microbeads (4.8%; PAC only; to our knowledge the first isolation of microbeads from marine megavertebrates). Fourier transform infrared spectroscopy (FT‐IR) of a subsample of particles (n = 169) showed a range of synthetic materials such as elastomers (MED: 61.2%; PAC: 3.4%), thermoplastics (ATL: 36.8%: MED: 20.7% PAC: 27.7%) and synthetic regenerated cellulosic fibres (SRCF; ATL: 63.2%: MED: 5.8% PAC: 68.9%). Synthetic particles being isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. These include exposure from polluted seawater and sediments and/or additional trophic transfer from contaminated prey/forage items. We assess the likelihood that microplastic ingestion presents a significant conservation problem at current levels compared to other anthropogenic threats
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