Antibody-dependent enhancement of severe dengue disease in humans

Katzelnick, Leah C.; Gresh, Lionel; Halloran, M. Elizabeth; Mercado, Juan Carlos; Kuan, Guillermina; Gordon, Aubree; Balmaseda, Ángel; Harris, Eva

doi:10.1126/science.aan6836

Cited by 938 publications

(1,002 citation statements)

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“…PRNT titers were also measured on a subset of 1,771 samples. HI titers correlate closely with PRNTs (Pearson correlation of 0.91) and with inhibition ELISAs, although titer values differ by laboratory and assay 6–9 .…”

mentioning

confidence: 86%

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Salje

Cummings

Rodríguez-Barraquer

et al. 2018

Nature

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243

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As with many pathogens, most dengue infections are subclinical and therefore unobserved1. Coupled with limited understanding of the dynamical behavior of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how they change over time, assay interpretation and cohort design. We develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 hemagglutination inhibition assay titer measurements)2,3. We identify 1,149 infections (95% CI: 1,135–1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. Post infection, individuals develop a stable setpoint antibody load after 1y that places them within or outside a risk window. Individuals with pre-existing titers of ≤1:40 develop hemorrhagic fever 7.4 (95% CI: 2.5–8.2) times as often as naïve individuals compared to 0.0 times for individuals with titers >1:40 (95% CI: 0.0–1.3). PRNT titers ≤1:100 were similarly associated with severe disease. Across the population, variability in the force of infection results in large-scale temporal changes in infection and disease risk that correlate poorly with age.

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mentioning

confidence: 86%

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Salje

Cummings

Rodríguez-Barraquer

et al. 2018

Nature

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243

261

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“…200–202 Recent work from the Ooi and Harris groups may provide an explanation for the difficulty in confirming ADE in human cases since it appears that the phenomenon may be only operative in a very narrow range of antibody titers. 189,190 …”

Section: Biochemistry and Molecular Biology Of Flavivirusesmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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“…С одной стороны, эти антитела, как правило, обладают высокой ви руснейтрализующей и протективной активностью, что может быть вызвано их способностью блокировать взаи-модействие домена D3 с клеточными рецепторами. С дру-гой стороны, антитела против домена D3 не склонны вы-зывать антителозависимое усиление инфекции, тогда как антитела к доменам D1 и D2, в частности антитела к петле слияния, могут усиливать инфекционность флавивирусов in vivo и приводить к усилению инфекции у людей (Dowd, Pierson, 2011;Halstead, 2014;Haslwanter et al, 2017;Katzelnick et al, 2017). Вместе с тем при иммунизации лю-дей большинство образующихся антител направлено на домены D1 и D2 (Oliphant et al, 2007;Crill et al, 2009;Wahala et al, 2009;Vratskikh et al, 2013;Jarmer et al, 2014).…”

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ANALYSIS OF DOMAIN SPECIFICITY OF THE PROTECTIVE CHIMERIC ANTIBODY ch14D5a AGAINST GLYCOPROTEIN E OF TICK-BORNE ENCEPHALITIS VIRUS

Baykov¹,

Emelyanova²,

Sokolova³

et al. 2018

Vestn. VOGiS

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A drug for the prevention and therapy of tick-borne encephalitis virus is being developed on the basis of the protective chimeric antibody ch14D5a. At the same time, the epitope recognized by this antibody on the surface of glycoprotein E has not been localized yet. The aim of this work was to identify the domain of glycoprotein E, to which the protective antibody ch14D5a binds. As a result, four recombinant variants of glycoprotein E were generated using the bacterial expression system: (1) the rE protein containing the domains D1, D2, and D3 of glycoprotein E; (2) the rED1+2 protein containing domains D1 and D2; (3) the rED3_301 protein, which is domain D3 of glycoprotein E, and (4) the rED3_294 protein comprising domain D3 and a hinge region connecting domains D1 and D3. The rED3_294 and rED3_301 proteins were obtained in soluble monomeric form. The rE and rED1+2 proteins were extracted from the inclusion bodies of Escherichia coli. Using Western blot analysis and surface plasmon resonance analysis, it was demonstrated that the protective chimeric antibody ch14D5a and its Fab fragment bound specifically to domain D3 of glycoprotein E. Since the antibodies recognizing epitopes on the surface of domain D3 do not tend to cause antibody-dependent enhancement of the infection as compared to antibodies directed to domains D1 and D2, the data obtained confirm the promise of using the antibody ch14D5a in the development of a therapeutic preparation against the tick-borne encephalitis virus.Key words: tick-borne encephalitis virus; glycoprotein E; domain D3; antibody; recombinant protein; surface plasmon resonance; epitope mapping. В настоящее время на основе протективного химерного анти-тела ch14D5a разрабатывается препарат для профилактики и терапии вируса клещевого энцефалита. Вместе с тем эпитоп, узнаваемый этим антителом на поверхности гликопротеина Е, не локализован. Для терапевтического использования анти-тела ch14D5a крайне желательно знать механизм действия этого антитела, в том числе узнаваемый им эпитоп. Целью данной работы было выявить домен гликопротеина Е, с кото-рым связывается протективное антитело ch14D5a. Для этого с использованием бактериальной системы экспрессии было получе но четыре рекомбинантных варианта гликопротеина Е: 1) белок rE, содержащий домены D1, D2 и D3 гликопротеина Е; 2) белок rED1+2, содержащий домены D1 и D2; 3) белок rED3_301, представляющий собой домен D3; 4) белок rED3_294, включа-ющий домен D3 и шарнирный участок, соединяющий доме-ны D1 и D3. Белки rED3_294 и rED3_301 были получены в рас-творимой мономерной форме, что подтверждено гель-фильт-рационной хроматографией. Белки rE и rED1+2 экстрагиро-ваны из телец включения. Методами вестерн-блот анализа и поверхностного плазмонного резонанса установлено, что протективное химерное антитело ch14D5a и его Fab-фрагмент связываются с доменом D3 и не связываются с доменами D1 и D2 гликопротеина Е вируса клещевого энцефалита. Поскольку антитела, узнающие эпитопы на поверхности домена D3, не склонны вызывать антителозависимое усиление инфе...

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Antibody-dependent enhancement of severe dengue disease in humans

Cited by 938 publications

References 95 publications

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Reconstruction of antibody dynamics and infection histories to evaluate dengue risk

Biochemistry and Molecular Biology of Flaviviruses

ANALYSIS OF DOMAIN SPECIFICITY OF THE PROTECTIVE CHIMERIC ANTIBODY ch14D5a AGAINST GLYCOPROTEIN E OF TICK-BORNE ENCEPHALITIS VIRUS

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