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  1. AU="Adrian V. Hill"
  2. AU="Du, Jialing"
  3. AU="Marion Migueres"
  4. AU="Sauka-Spengler, Tatjana"
  5. AU="Košir, Mitja"
  6. AU="Narro, Carla"
  7. AU="Antunes-Meireles, Pedro"

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  1. Article ; Online: A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

    Anna L Goodman / Andrew M Blagborough / Sumi Biswas / Yimin Wu / Adrian V Hill / Robert E Sinden / Simon J Draper

    PLoS ONE, Vol 6, Iss 12, p e

    2011  Volume 29428

    Abstract: The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant ... ...

    Abstract The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit vaccines.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570 ; 572
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Correction

    Kelli K. Ryckman / Katherine Fielding / Adrian V. Hill / Maimuna Mendy / Pura Rayco-Solon / Giorgio Sirugo / Marianne A. van der Sande / Pauline Waight / Hilton C. Whittle / Andrew J. Hall / Scott M. Williams / Branwen J. Hennig

    PLoS ONE, Vol 6, Iss

    Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis.

    2011  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Correction

    Branwen J. Hennig / Katherine Fielding / John Broxholme / Mathurin Diatta / Maimuna Mendy / Catrin Moore / Andrew J. Pollard / Pura Rayco-Solon / Giorgio Sirugo / Marianne A. van der Sande / Pauline Waight / Hilton C. Whittle / Syed M. Zaman / Adrian V. Hill / Andrew J. Hall

    PLoS ONE, Vol 6, Iss

    Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus Infection

    2011  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Correction

    Branwen J. Hennig / Katherine Fielding / John Broxholme / Mathurin Diatta / Maimuna Mendy / Catrin Moore / Andrew J. Pollard / Pura Rayco-Solon / Giorgio Sirugo / Marianne A. van der Sande / Pauline Waight / Hilton C. Whittle / Syed M. Zaman / Adrian V. Hill / Andrew J. Hall

    PLoS ONE, Vol 6, Iss

    Host Genetic Factors and Vaccine-Induced Immunity to Hepatitis B Virus Infection.

    2011  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Correction

    Kelli K. Ryckman / Katherine Fielding / Adrian V. Hill / Maimuna Mendy / Pura Rayco-Solon / Giorgio Sirugo / Marianne A. van der Sande / Pauline Waight / Hilton C. Whittle / Andrew J. Hall / Scott M. Williams / Branwen J. Hennig

    PLoS ONE, Vol 6, Iss

    Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis

    2011  Volume 2

    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2011-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Host genetic factors and vaccine-induced immunity to HBV infection

    Kelli K Ryckman / Katherine Fielding / Adrian V Hill / Maimuna Mendy / Pura Rayco-Solon / Giorgio Sirugo / Marianne A van der Sande / Pauline Waight / Hilton C Whittle / Andrew J Hall / Scott M Williams / Branwen J Hennig

    PLoS ONE, Vol 5, Iss 8, p e

    haplotype analysis.

    2010  Volume 12273

    Abstract: Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak ... ...

    Abstract Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1x10(-5) for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2010-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Progression of Plasmodium berghei through Anopheles stephensi is density-dependent.

    Robert E Sinden / Emma J Dawes / Yasmene Alavi / Joanna Waldock / Olivia Finney / Jacqui Mendoza / Geoff A Butcher / Laura Andrews / Adrian V Hill / Sarah C Gilbert / María-Gloria Basáñez

    PLoS Pathogens, Vol 3, Iss 12, p e

    2007  Volume 195

    Abstract: It is well documented that the density of Plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. It is less clear that parasite density in the mosquito regulates survival ...

    Abstract It is well documented that the density of Plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. It is less clear that parasite density in the mosquito regulates survival and transmission of this important pathogen. Numerous studies have described conversion rates of Plasmodium from one life stage to the next within the mosquito, yet few have considered that these rates might vary with parasite density. Here we establish infections with defined numbers of the rodent malaria parasite Plasmodium berghei to examine how parasite density at each stage of development (gametocytes; ookinetes; oocysts and sporozoites) influences development to the ensuing stage in Anopheles stephensi, and thus the delivery of infectious sporozoites to the vertebrate host. We show that every developmental transition exhibits strong density dependence, with numbers of the ensuing stages saturating at high density. We further show that when fed ookinetes at very low densities, oocyst development is facilitated by increasing ookinete number (i.e., the efficiency of ookinete-oocyst transformation follows a sigmoid relationship). We discuss how observations on this model system generate important hypotheses for the understanding of malaria biology, and how these might guide the rational analysis of interventions against the transmission of the malaria parasites of humans by their diverse vector species.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2007-12-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Host genetic factors and vaccine-induced immunity to hepatitis B virus infection.

    Branwen J Hennig / Katherine Fielding / John Broxholme / Mathurin Diatta / Maimuna Mendy / Catrin Moore / Andrew J Pollard / Pura Rayco-Solon / Giorgio Sirugo / Marianne A van der Sande / Pauline Waight / Hilton C Whittle / Syed M Zaman / Adrian V Hill / Andrew J Hall

    PLoS ONE, Vol 3, Iss 3, p e

    2008  Volume 1898

    Abstract: Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent ... ...

    Abstract Vaccination against hepatitis B virus infection (HBV) is safe and effective; however, vaccine-induced antibody level wanes over time. Peak vaccine-induced anti-HBs level is directly related to antibody decay, as well as risk of infection and persistent carriage despite vaccination. We investigated the role of host genetic factors in long-term immunity against HBV infection based on peak anti-HBs level and seroconversion to anti-HBc.We analyzed 715 SNP across 133 candidate genes in 662 infant vaccinees from The Gambia, assessing peak vaccine-induced anti-HBs level and core antibody (anti-HBc) status, whilst adjusting for covariates. A replication study comprised 43 SNPs in a further 393 individuals.In our initial screen we found variation in IFNG, MAPK8, and IL10RA to affect peak anti-HBs level (GMTratio of < 0.6 or > 1.5 and P < or = 0.001) and lesser associations in other genes. Odds of core-conversion was associated with variation in CD163. A coding change in ITGAL (R719V) with likely functional relevance showed evidence of association with increased peak anti-HBs level in both screens (1st screen: s595_22 GMTratio 1.71, P = 0.013; 2nd screen: s595_22 GMTratio 2.15, P = 0.011).This is to our knowledge the largest study to date assessing genetic determinants of HBV vaccine-induced immunity. We report on associations with anti-HBs level, which is directly related to durability of antibody level and predictive of vaccine efficacy long-term. A coding change in ITGAL, which plays a central role in immune cell interaction, was shown to exert beneficial effects on induction of peak antibody level in response to HBV vaccination. Variation in this gene does not appear to have been studied in relation to immune responses to viral or vaccine challenges previously. Our findings suggest that genetic variation in loci other than the HLA region affect immunity induced by HBV vaccination.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2008-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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