Broadly neutralizing human antibodies against dengue virus identified by single B cell transcriptomics

Eliciting broadly neutralizing antibodies (bNAbs) against the four dengue virus serotypes (DENV1-4) that are spreading into new territories is an important goal of vaccine design. To define bNAb targets, we characterized 28 antibodies belonging to expanded and hypermutated clonal families identified by transcriptomic analysis of single plasmablasts from DENV-infected individuals. Among these, we identified J9 and J8, two somatically related bNAbs that potently neutralized DENV1-4. Mutagenesis studies showed that the major recognition determinants of these bNAbs are in E protein domain I, distinct from the only known class of human bNAbs against DENV with a well-defined epitope. B cell repertoire analysis from acute-phase peripheral blood suggested that J9 and J8 followed divergent somatic hypermutation pathways, and that a limited number of mutations was sufficient for neutralizing activity. Our study suggests multiple B cell evolutionary pathways leading to DENV bNAbs targeting a new epitope that can be exploited for vaccine design.
Source: eLife - Category: Biomedical Science Tags: Immunology and Inflammation Microbiology and Infectious Disease Source Type: research

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(CUNY Graduate School of Public Health and Health Policy) A new study led by researchers at the CUNY Graduate School of Public Health and Health Policy (CUNY SPH) and the National School of Tropical Medicine at Baylor College of Medicine found that routinely giving the Zika vaccine to women of childbearing age could save money if the risk of Zika is around that of other mosquito-borne diseases like dengue and chikungunya.
Source: EurekAlert! - Infectious and Emerging Diseases - Category: Infectious Diseases Source Type: news
West Nile (WN) virus infection of humans is frequently asymptomatic, but can also lead to WN fever or neuroinvasive disease. CD4 T cells and B cells are critical in the defense against WN virus, and neutralizing antibodies, which are directed against the viral glycoprotein E, are an accepted correlate of protection. For the efficient production of these antibodies, B cells interact directly with CD4 helper T cells that recognize peptides from E or the two other structural proteins (capsid-C and membrane-prM/M) of the virus. However, the specific protein sites yielding such helper epitopes remain unknown. Here, we explored ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Abstract Difficulties inherent in the identification of immune correlates of protection or severe disease have challenged the development and evaluation of dengue vaccines. There persist substantial gaps in knowledge about the complex effects of age and sequential dengue virus (DENV) exposures on these correlations. To address these gaps, we are conducting a novel family-based cohort-cluster study for DENV transmission in Kamphaeng Phet, Thailand. The study began in 2015 and is funded until at least 2023. As of May 2019, 2870 individuals in 485 families are actively enrolled. The families comprise at least one chi...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
Abstract Dengue virus (DENV) and Zika virus (ZIKV) are antigenically related mosquito-transmitted viruses which represent a big public health problem. Although the antigenic cross-reactivity between two viruses were intensively investigated at the antibody and T cell levels, how DENV envelope protein domain III (EDIII)-elicited antibodies (Abs) impact the outcome of ZIKV infection is uncertain. Here, our results show that the sera isolated from DENV-EDIII-immunized wild-type mice recognized ZIKV-EDIII and cross-neutralized ZIKV in vitro. Passive transfer of DENV-EDIII-immune sera protected 1-day-old mice against l...
Source: Virus Research - Category: Virology Authors: Tags: Virus Res Source Type: research
Researchers have reported that a new vaccine against the dengue virus protected children and adolescents in a phase 3 trial conducted in Asia and Latin America.
Source: JAMA - Category: General Medicine Source Type: research
Conclusions/SignificanceAchieving high uptake and compliance with PPT in populations most at risk of adverse outcomes from Zika infection requires engaging key users in open dialogue to identify and address any practical issues regarding PPT use, and concerns over safety. The findings presented here suggest that educational campaigns should strongly emphasize the risks associated with Zika during pregnancy, and discuss safety profiles of approved synthetic repellents and the availability of EPA-approved plant-based repellents. In addition, the economic and political context should be a major consideration when evaluating p...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
by Anne L. Wilson, Orin Courtenay, Louise A. Kelly-Hope, Thomas W. Scott, Willem Takken, Steve J. Torr, Steve W. Lindsay Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis exert a huge burden of morbidity and mortality worldwide, particularly affecting the poorest of the poor. The principal method by which these diseases are controlled is through vector control, which has a long and distinguishe d history. Vector control, to a greater extent than drugs or vaccines, has been responsible for shrinking the map of many VBDs. Here, we describe the history of vector control programmes worldwide from the lat...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract In this paper we introduce a single serotype transmission model, including an age-dependent mosquito biting rate, to find the optimal vaccination age against dengue in Brazil with Dengvaxia. The optimal vaccination age and minimal lifetime expected risk of hospitalisation are found by adapting a method due to Hethcote (Math Biosci 89:29-52). Any number and combination of the four dengue serotypes DENv1-4 is considered. Successful vaccination against a serotype corresponds to a silent infection. The effects of antibody-dependent enhancement (ADE) and permanent cross-immunity after two heterologous infectio...
Source: Bulletin of Mathematical Biology - Category: Bioinformatics Authors: Tags: Bull Math Biol Source Type: research
Publication date: Available online 10 January 2020Source: Antiviral ResearchAuthor(s): Elizabeth C. Clarke, Steven B. BradfuteAbstractFor more than 20 years, researchers have used laboratory mice lacking type I or both type I and type II interferon (IFN) responses to study viruses that cause hemorrhagic fever (HF) in humans. Whereas immunocompetent mice do not become ill when infected with Ebola, Lassa, dengue and other HF viruses, IFN-deficient mice typically develop severe or fatal disease when inoculated with these pathogens. The ease of employment of these “mouse models” has led to their extensive use in bi...
Source: Antiviral Therapy - Category: Virology Source Type: research
Abstract For more than 20 years, researchers have used laboratory mice lacking type I or both type I and type II interferon (IFN) responses to study viruses that cause hemorrhagic fever (HF) in humans. Whereas immunocompetent mice do not become ill when infected with Ebola, Lassa, dengue and other HF viruses, IFN-deficient mice typically develop severe or fatal disease when inoculated with these pathogens. The ease of employment of these "mouse models" has led to their extensive use in biocontainment laboratories to assess the efficacy of novel vaccines, often without consideration of whether adaptive im...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
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