Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Title: Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Authors: Rouvinski A, Guardado-Calvo P, Barba-Spaeth G, Duquerroy S, Vaney MC, Kikuti CM, Navarro Sanchez ME, Dejnirattisai W, Wongwiwat W, Haouz A, Girard-Blanc C, Petres S, Shepard WE, Desprès P, Arenzana-Seisdedos F, Dussart P, Mongkolsapaya J, Screaton GR, Rey FA

Publisher: Nature

Year: 2015

Keywords: X-ray crystallography

Abstract

Dengue disease is caused by four different flavivirus serotypes, which infect 390 million people yearly with 25% symptomatic cases 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. Structural studies so far have characterized only epitopes recognized by serotype-specific human antibodies. We recently isolated human antibodies potently neutralizing all four dengue virus serotypes. 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 loop 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 cell, 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.

References:
Rouvinski A, Guardado-Calvo P, Barba-Spaeth G, Duquerroy S, Vaney MC, Kikuti CM, Navarro Sanchez ME, Dejnirattisai W, Wongwiwat W, Haouz A, Girard-Blanc C, Petres S, Shepard WE, Desprès P, Arenzana-Seisdedos F, Dussart P, Mongkolsapaya J, Screaton GR, Rey FA. Recognition determinants of broadly neutralizing human antibodies against dengue viruses. Nature 2015, Apr 2; 520 (7545):109-13.

Doi: http://dx.doi.org/10.1038/nature14130

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New insights into the immunopathology and control of dengue virus infection

Title: New insights into the immunopathology and control of dengue virus infection

Authors: Screaton G, Mongkolsapaya J, Yacoub S, Roberts C.
Publisher: Nature Review Immunology
Year: 2015

Abstract

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.

References:
Screaton G, Mongkolsapaya J, Yacoub S, Roberts C., New insights into the immunopathology and control of dengue virus infection. Nature Review Immunology 2015, Nov 25; 15(12):745-59

Doi: http://dx.doi.org/10.1038/nri3916

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Dengue research funded by the European Commission-scientific strategies of three European dengue research consortia

Title: Dengue research funded by the European Commission-scientific strategies of three European dengue research consortia

Authors: Jaenisch T (IDAMS), Sakuntabhai A (DENFREE), Wilder-Smith A (DengueTools)
Publisher: PLoS Neglected Tropical Diseases
Year: 2013

Abstract

Dengue has been neglected for many years. Major research gaps for dengue exist in the areas of epidemiology under changing climate conditions, clinical management, pathogenesis, vector control, surveillance and response, vaccines, drugs, and health policy research. The European Commission (EC) launched a call under the Seventh Framework Programme with the title of “Comprehensive control of Dengue fever under changing climatic conditions”. The funding of such a large and complex research programme focusing on a single disease highlights the emphasis that the European Commission has put on dengue and its potential threat to Europe. In this paper, we present these three consortia and outline their scientific strategies and potential role within the international dengue research community.

References:
Jaenisch T (IDAMS), Sakuntabhai A (DENFREE), Wilder-Smith A (DengueTools), Dengue research funded by the European Commission-scientific strategies of three European dengue research consortia, PLoS Neglected Tropical Diseases, 2013, Dec 12; 7(12):e2320

Doi: http://dx.doi.org/10.1371/journal.pntd.0002320

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Dengue expansion in Africa-not recognized or not happening?

Title: Dengue expansion in Africa-not recognized or not happening?

Authors: Jaenisch T, Junghanss T, Wills B, Brady OJ, Eckerle I, Farlow A, Hay SI, McCall PJ, Messina JP, Ofula V, Sall AA, Sakuntabhai A, Velayudhan R, Wint GR, Zeller H, Margolis HS, Sankoh O
Publisher: Emerging Infectious Diseases
Year: 2014

Abstract

An expert conference on Dengue in Africa was held in Accra, Ghana, in February 2013 to consider key questions regarding the possible expansion of dengue in Africa. Four key action points were highlighted to advance our understanding of the epidemiology of dengue in Africa. First, dengue diagnostic tools must be made more widely available in the healthcare setting in Africa. Second, representative data need to be collected across Africa to uncover the true burden of dengue. Third, established networks should collaborate to produce these types of data. Fourth, policy needs to be informed so the necessary steps can be taken to provide dengue vector control and health services.

References:
Jaenisch T, Junghanss T, Wills B, Brady OJ, Eckerle I, Farlow A, Hay SI, McCall PJ, Messina JP, Ofula V, Sall AA, Sakuntabhai A, Velayudhan R, Wint GR, Zeller H, Margolis HS, Sankoh O, Dengue expansion in Africa-not recognized or not happening? Emerging Infectious Diseases 2014, Oct; 20(10)

Doi: http://dx.doi.org/10.3201/eid2010.140487

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Mosquito control might not bolster imperfect dengue vaccines

Title: Mosquito control might not bolster imperfect dengue vaccines

Authors: Paul R, Sousa C, Sakuntabhai A, Devine G.
Publisher: Lancet
Year: 2014

Abstract

The most recent dengue vaccine trial data from Asia claims 40–70% efficacy in children aged 2–14 years. This is a substantial advance in dengue prevention but clearly falls short of the levels of protection required for a standalone intervention. The dengue vaccine initiative and other consortia have emphasised the benefits of integrating vaccines with mosquito control measures which infers that vector control can bolster the effect of imperfect vaccines.

References:
Paul R, Sousa C, Sakuntabhai A, Devine G., Mosquito control might not bolster imperfect dengue vaccines Lancet. 2014, Nov 15; 384(9956):1747-8

Doi: http://dx.doi.org/10.1016/S0140-6736(14)62071-7

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