Imperial College London

ProfessorGavinScreaton

Faculty of MedicineDepartment of Immunology and Inflammation

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 1190g.screaton Website

 
 
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Assistant

 

Ms Claire Puddephatt +44 (0)20 7594 1190

 
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Location

 

2.15Faculty BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

142 results found

Screaton G, Mongkolsapaya J, Yacoub S, Roberts Cet al., 2015, New insights into the immunopathology and control of dengue virus infection, Nature Reviews Immunology, Vol: 15, Pages: 745-759, ISSN: 1474-1741

Dengue virus poses a major threat to global public health: two-thirds of the world's population is now at risk from infection by this mosquito-borne virus. Dengue virus causes a range of diseases with a small proportion of infected patients developing severe plasma leakage that leads to dengue shock syndrome, organ impairment and bleeding. Infection with one of the four viral serotypes results in the development of homotypic immunity to that serotype. However, subsequent infection with a different serotype is associated with an increased risk of developing severe disease, which has led to the suggestion that severe disease is triggered by immunopathology. This Review outlines recent advances in the understanding of immunopathology, vaccine development and human monoclonal antibodies produced against dengue virus.

Journal article

Dejnirattisai W, Wongwiwat W, Supasa S, Zhang X, Dai X, Rouvinsky A, Jumnainsong A, Edwards C, Nguyen THQ, Duangchinda T, Grimes JM, Tsai W-Y, Lai C-Y, Wang W-K, Malasit P, Farrar J, Simmons CP, Zhou ZH, Rey FA, Mongkolsapaya J, Screaton GRet al., 2015, A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus (vol 16, pg 171, 2015), NATURE IMMUNOLOGY, Vol: 16, Pages: 785-785, ISSN: 1529-2908

Journal article

Dejnirattisai W, Wongwiwat W, Supasa S, Zhang X, Dai X, Rouvinski A, Jumnainsong A, Edwards C, Quyen NTH, Duangchinda T, Grimes JM, Tsai W-Y, Lai C-Y, Wang W-K, Malasit P, Farrar J, Simmons CP, Zhou ZH, Rey FA, Mongkolsapaya J, Screaton GRet al., 2015, A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus (vol 16, pg 170, 2015), NATURE IMMUNOLOGY, Vol: 16, Pages: 544-544, ISSN: 1529-2908

Journal article

Yacoub S, Wertheim H, Simmons CP, Screaton G, Wills Bet al., 2015, Microvascular and endothelial function for risk prediction in dengue: an observational study, LANCET, Vol: 385, Pages: 102-102, ISSN: 0140-6736

Journal article

Rouvinski A, Guardado-Calvo P, Barba-Spaeth G, Duquerroy S, Vaney M-C, Kikuti CM, Sanchez MEN, Dejnirattisai W, Wongwiwat W, Haouz A, Girard-Blanc C, Petres S, Shepard WE, Despres P, Arenzana-Seisdedos F, Dussart P, Mongkolsapaya J, Screaton GR, Rey FAet al., 2015, Recognition determinants of broadly neutralizing human antibodies against dengue viruses, Nature, Vol: 520, Pages: 109-113, ISSN: 0028-0836

Dengue disease is caused by four different flavivirus1 serotypes, which infect 390 million people yearly with 25% symptomatic cases2 and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (refs 3, 4). Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies5, 6. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes7. Here we describe the X-ray structures of four of these broadly neutralizing antibodies in complex with the envelope glycoprotein E from dengue virus serotype 2, revealing that the recognition determinants are at a serotype-invariant site at the E-dimer interface, including the exposed main chain of the E fusion loop8 and the two conserved glycan chains. This ‘E-dimer-dependent epitope’ is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell9, explaining its conservation across serotypes and highlighting an Achilles’ heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.

Journal article

Dejnirattisai W, Wongwiwat W, Supasa S, Zhang X, Dai X, Rouvinsky A, Jumnainsong A, Edwards C, Nguyen THQ, Duangchinda T, Grimes JM, Tsai W-Y, Lai C-Y, Wang W-K, Malasit P, Farrar J, Simmons CP, Zhou ZH, Rey FA, Mongkolsapaya J, Screaton GRet al., 2014, A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus, Nature Immunology, Vol: 16, Pages: 170-177, ISSN: 1529-2916

Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

Journal article

Screaton GR, 2014, International Congress on Medical Virology 2014 (ICMV 2014), International Congress on Medical Virology 2014

Protective and pathogenic immunity in dengue virus infectionGavin Screaton, Dept. of Medicine, Imperial College LondonDengue is a mosquito borne virus infection occurring in tropical and subtropical countries. There are estimated to be around 400 million infections annually of which approximately one quarter are clinically apparent. The majority of these result in a self limited, but non the less unpleasant febrile illness, dengue fever. 1-5% of infections lead to a more severe disease, dengue haemorrhagic fever, which is characterized by a severe vascular leak, hypovolaemia and in extreme cases shock and haemorrhage. Dengue exists as four highly divergent serotypes differing in sequence by some 30-35%; infection with one serotype does not provide protection against the other three. In endemic areas serotypes frequently co-circulate and repeat infections are common. Interestingly, severe disease is much more common in secondary as opposed to primary infections, implying a role of the acquired immune system in disease pathogenesis. Understanding this immune enhancement of disease is crucial for the design of safe and effective vaccines. Through clinical collaborations in Thailand and Vietnam we have been studying the immune response to dengue in cohorts of infected children and will describe components of T cell and antibody mediated immunity and their potential to enhance or protect from dengue infection.

Conference paper

Decembre E, Assil S, Hillaire MLB, Dejnirattisai W, Mongkolsapaya J, Screaton GR, Davidson AD, Dreux Met al., 2014, Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366

Journal article

Mongkolsapaya J, Screaton GR, 2014, The Acquired Response in Dengue Virus Infection, Dengue and Dengue Hemorrhagic Fever, 2nd Edition, Editors: Gubler, Farrar, Eong Ooi, Vasudevan, Publisher: CABI, Pages: 249-267, ISBN: 9781845939649

Recent exciting research on dengue has resulted in major advances in our understanding of all aspects of the biology of these viruses, and this updated second edition brings together leading research and clinical scientists to review dengue ...

Book chapter

Gubler DJ, Ooi EE, Vasudevan S, Farrar Jet al., 2014, Dengue and Dengue Hemorrhagic Fever, 2nd Edition, Publisher: CABI, ISBN: 9781845939649

References. Araujo, F.M., Araujo, M.S., Nogueira, R.M., Brilhante, R.S., Oliveira, D.N., Rocha, M.F., Cordeiro, R.A., Araújo, R.M. and Sidrim, J.J. (2012) Central nervous system involvement in dengue: a study in fatal cases from a dengue ...

Book

Matangkasombut P, Chan-in W, Opasawaschai A, Pongchaikul P, Tangthawornchaikul N, Vasanawathana S, Limpitikul W, Malasit P, Duangchinda T, Screaton G, Mongkolsapaya Jet al., 2014, Invariant NKT Cell Response to Dengue Virus Infection in Human, PLOS NEGLECTED TROPICAL DISEASES, Vol: 8, ISSN: 1935-2735

Journal article

Yacoub S, Wertheim H, Simmons CP, Screaton G, Wills Bet al., 2014, Cardiovascular manifestations of the emerging dengue pandemic, NATURE REVIEWS CARDIOLOGY, Vol: 11, Pages: 335-345, ISSN: 1759-5002

Journal article

Jaenisch T, IDAMS, Sakuntabhai A, DENFREE, Wilder-Smith A, DengueToolset al., 2013, Dengue Research Funded by the European Commission-Scientific Strategies of Three European Dengue Research Consortia, PLOS Neglected Tropical Diseases, Vol: 7, ISSN: 1935-2735

Journal article

Tsai W-Y, Lai C-Y, Wu Y-C, Lin H-E, Edwards C, Jumnainsong A, Kliks S, Halstead S, Mongkolsapaya J, Screaton GR, Wang W-Ket al., 2013, High-Avidity and Potently Neutralizing Cross-Reactive Human Monoclonal Antibodies Derived from Secondary Dengue Virus Infection, JOURNAL OF VIROLOGY, Vol: 87, Pages: 12562-12575, ISSN: 0022-538X

Journal article

Roberts CH, Mongkolsapaya J, Screaton G, 2013, New opportunities for control of dengue virus, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 26, Pages: 567-574, ISSN: 0951-7375

Journal article

Siridechadilok B, Gomutsukhavadee M, Sawaengpol T, Sangiambut S, Puttikhunt C, Chin-inmanu K, Suriyaphol P, Malasit P, Screaton G, Mongkolsapaya Jet al., 2013, A Simplified Positive-Sense-RNA Virus Construction Approach That Enhances Analysis Throughput, Journal of Virology, Vol: 87, Pages: 12667-12674, ISSN: 1098-5514

Here we present an approach that advances the throughput of a genetic analysis of a positive-sense RNA virus by simplifying virus construction. It enabled comprehensive dissection of a complex, multigene phenotype through rapid derivation of a large number of chimeric viruses and construction of a mutant library directly from a virus pool. The versatility of the approach described here expands the applicability of diverse genetic approaches to study these viruses.

Journal article

Kraivong R, Vasanawathana S, Limpitikul W, Malasit P, Tangthawornchaikul N, Botto M, Screaton GR, Mongkolsapaya J, Pickering MCet al., 2013, Complement alternative pathway genetic variation and Dengue infection in the Thai population, Clinical and Experimental Immunology, Vol: 174, Pages: 326-334, ISSN: 1365-2249

Dengue disease is a mosquito-borne infection caused by Dengue virus. Infection may be asymptomatic or variably manifest as mild Dengue fever (DF) to the most severe form, Dengue haemorrhagic fever (DHF). Mechanisms that influence disease severity are not understood. Complement, an integral component of the immune system, is activated during Dengue infection and the degree of activation increases with disease severity. Activation of the complement alternative pathway is influenced by polymorphisms within activation (factor B rs12614/rs641153, C3 rs2230199) and regulatory [complement factor H (CFH) rs800292] proteins, collectively termed a complotype. Here, we tested the hypothesis that the complotype influences disease severity during secondary Dengue infection. In addition to the complotype, we also assessed two other disease-associated CFH polymorphisms (rs1061170, rs3753394) and a structural polymorphism within the CFH protein family. We did not detect any significant association between the examined polymorphisms and Dengue infection severity in the Thai population. However, the minor allele frequencies of the factor B and C3 polymorphisms were less than 10%, so our study was not sufficiently powered to detect an association at these loci. We were also unable to detect a direct interaction between CFH and Dengue NS1 using both recombinant NS1 and DV2-infected culture supernatants. We conclude that the complotype does not influence secondary Dengue infection severity in the Thai population.

Journal article

Yacoub S, Mongkolsapaya J, Screaton G, 2013, The pathogenesis of dengue, CURRENT OPINION IN INFECTIOUS DISEASES, Vol: 26, Pages: 284-289, ISSN: 0951-7375

Journal article

Li D, Hong A, Lu Q, Gao GF, Jin B, Screaton GR, Xu X-Net al., 2012, A novel role of CD1c in regulating CD1d-mediated NKT cell recognition by competitive binding to Ig-like transcript 4, INTERNATIONAL IMMUNOLOGY, Vol: 24, Pages: 729-737, ISSN: 0953-8178

Journal article

Midgey CM, Flanagan A, Hai BT, Dejnirattisai W, Chawansuntati K, Jumnainsong A, Wongwiwat W, Duangchinda T, Mongkolsapaya J, Grimes JM, Screaton GRet al., 2012, Structural Analysis of a Dengue Cross-Reactive Antibody Complexed with Envelope Domain III Reveals the Molecular Basis of Cross-Reactivity, JOURNAL OF IMMUNOLOGY, Vol: 188, Pages: 4971-4979, ISSN: 0022-1767

Journal article

Roberts CH, Mongkolsapaya J, Screaton G, 2012, Dengue fever: a practical guide, BRITISH JOURNAL OF HOSPITAL MEDICINE, Vol: 73, Pages: C60-C64, ISSN: 1750-8460

Journal article

Midgley CM, Bajwa-Joseph M, Vasanawathana S, Limpitikul W, Wills B, Flanagan A, Waiyaiya E, Hai BT, Cowper AE, Chotiyarnwong P, Grimes JM, Yoksan S, Malasit P, Simmons CP, Mongkolsapaya J, Screaton GRet al., 2011, An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection (vol 85, pg 410, 2011), JOURNAL OF VIROLOGY, Vol: 85, Pages: 12100-12100, ISSN: 0022-538X

Journal article

Watson AA, Lebedev AA, Hall BA, Fenton-May AE, Vagin AA, Dejnirattisai W, Felce J, Mongkolsapaya J, Palma AS, Liu Y, Feizi T, Screaton GR, Murshudov GN, O'Callaghan CAet al., 2011, Structural flexibility of the macrophage dengue virus receptor CLEC5A: implications for ligand binding and signaling, J.Biol.Chem., Vol: 286, Pages: 24208-24218

The human C-type lectin-like molecule CLEC5A is a critical macrophage receptor for dengue virus. The binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule DAP12, stimulating proinflammatory cytokine release. We have crystallized an informative ensemble of CLEC5A structural conformers at 1.9-A resolution and demonstrate how an on-off extension to a beta-sheet acts as a binary switch regulating the flexibility of the molecule. This structural information together with molecular dynamics simulations suggests a mechanism whereby extracellular events may be transmitted through the membrane and influence DAP12 signaling. We demonstrate that CLEC5A is homodimeric at the cell surface and binds to dengue virus serotypes 1-4. We used blotting experiments, surface analyses, glycan microarray, and docking studies to investigate the ligand binding potential of CLEC5A with particular respect to dengue virus. This study provides a rational foundation for understanding the dengue virus-macrophage interaction and the role of CLEC5A in dengue virus-induced lethal disease

Journal article

Dejnirattisai W, Webb AI, Chan V, Jumnainsong A, Davidson A, Mongkolsapaya J, Screaton Get al., 2011, Lectin Switching During Dengue Virus Infection, JOURNAL OF INFECTIOUS DISEASES, Vol: 203, Pages: 1775-1783, ISSN: 0022-1899

Journal article

Dejnirattisai W, Malasit P, Mongkolsapaya J, Screaton Get al., 2011, Antibody responses to dengue infection, JOURNAL OF IMMUNOLOGY, Vol: 186, ISSN: 0022-1767

Journal article

Midgley CM, Bajwa-Joseph M, Vasanawathana S, Limpitikul W, Wills B, Flanagan A, Waiyaiya E, Tran HB, Cowper AE, Chotiyarnwon P, Grimes JM, Yoksan S, Malasit P, Simmons CP, Mongkolsapaya J, Screaton GRet al., 2011, An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection, JOURNAL OF VIROLOGY, Vol: 85, Pages: 410-421, ISSN: 0022-538X

Journal article

Screaton G, 2010, Immunopathology in dengue virus infection, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 9-10, ISSN: 0019-2805

Conference paper

Duangchinda T, Dejnirattisai W, Vasanawathana S, Limpitikul W, Tangthawornchaikul N, Malasit P, Mongkolsapaya J, Screaton Get al., 2010, Immunodominant T-cell responses to dengue virus NS3 are associated with DHF, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 16922-16927, ISSN: 0027-8424

Journal article

Weng L, Williams RO, Vieira PL, Screaton G, Feldmann M, Dazzi Fet al., 2010, The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity, ANNALS OF THE RHEUMATIC DISEASES, Vol: 69, Pages: 1519-1526, ISSN: 0003-4967

Journal article

Dejnirattisai W, Jumnainsong A, Onsirisakul N, Fitton P, Vasanawathana S, Limpitikul W, Puttikhunt C, Edwards C, Duangchinda T, Supasa S, Chawansuntati K, Malasit P, Mongkolsapaya J, Screaton Get al., 2010, Cross-Reacting Antibodies Enhance Dengue Virus Infection in Humans, SCIENCE, Vol: 328, Pages: 745-748, ISSN: 0036-8075

Journal article

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