Longitudinal Analysis of the Human B Cell Response to Ebola Virus Infection

Publication date: Available online 16 May 2019Source: CellAuthor(s): Carl W. Davis, Katherine J.L. Jackson, Anita K. McElroy, Peter Halfmann, Jessica Huang, Chakravarthy Chennareddy, Ashley E. Piper, Yvonne Leung, César G. Albariño, Ian Crozier, Ali H. Ellebedy, John Sidney, Alessandro Sette, Tianwei Yu, Sandra C.A. Nielsen, Arthur J. Goff, Christina F. Spiropoulou, Erica Ollman Saphire, Guy Cavet, Yoshihiro KawaokaSummaryEbola virus (EBOV) remains a public health threat. We performed a longitudinal study of B cell responses to EBOV in four survivors of the 2014 West African outbreak. Infection induced lasting EBOV-specific immunoglobulin G (IgG) antibodies, but their subclass composition changed over time, with IgG1 persisting, IgG3 rapidly declining, and IgG4 appearing late. Striking changes occurred in the immunoglobulin repertoire, with massive recruitment of naive B cells that subsequently underwent hypermutation. We characterized a large panel of EBOV glycoprotein-specific monoclonal antibodies (mAbs). Only a small subset of mAbs that bound glycoprotein by ELISA recognized cell-surface glycoprotein. However, this subset contained all neutralizing mAbs. Several mAbs protected against EBOV disease in animals, including one mAb that targeted an epitope under evolutionary selection during the 2014 outbreak. Convergent antibody evolution was seen across multiple donors, particularly among VH3-13 neutralizing antibodies specific for the GP1 core. Our study provi...
Source: Cell - Category: Cytology Source Type: research

Related Links:

Abstract In this two-part series of reviews, we have invited experts in their fields to contribute articles on the status of vaccine research and development for emerging pathogens. This topic has been brought into sharp focus in recent years following significant outbreaks of viral diseases such as those causing severe acute respiratory syndrome and Middle East respiratory syndrome, as well as devastating outbreaks of diseases caused by the Ebola, Marburg, Zika and Lassa fever viruses, to name only a few examples. Additionally, bacterial infections leading to bubonic and pneumonic plague, most notably in Madagasc...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research
In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC50) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC50)> 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Rui Dong1, Lily He1, Rong Lucy He2 and Stephen S.-T. Yau1* 1Department of Mathematical Sciences, Tsinghua University, Beijing, China 2Department of Biological Sciences, Chicago State University, Chicago, IL, United States Classification of DNA sequences is an important issue in the bioinformatics study, yet most existing methods for phylogenetic analysis including Multiple Sequence Alignment (MSA) are time-consuming and computationally expensive. The alignment-free methods are popular nowadays, whereas the manual intervention in those methods usually decreases the accuracy. Also, the interactions among nucleotid...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Vaccination remains the most successful and effective mechanism of pathogen control. However, their development and deployment in epidemic settings have been limited, and the 2015 Ebola outbreak in West Africa identified several bottlenecks linked to a lack of investment in pathogen research, infrastructure or regulation. Shortly after this outbreak, the UK Government established the UK Vaccine Network to ensure the UK is better prepared to respond to pathogens outbreaks of epidemic potential. As part of their work, the network commissioned the creation of a Vaccine Development Tool (http://www.vaccinedev...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Viruses, Vol. 11, Pages 137: Filovirus Virulence in Interferon α/β and γ Double Knockout Mice, and Treatment with Favipiravir Viruses doi: 10.3390/v11020137 Authors: Jason E. Comer Olivier Escaffre Natasha Neef Trevor Brasel Terry L. Juelich Jennifer K. Smith Jeanon Smith Birte Kalveram David D. Perez Shane Massey Lihong Zhang Alexander N. Freiberg The 2014 Ebolavirus outbreak in West Africa highlighted the need for vaccines and therapeutics to prevent and treat filovirus infections. A well-characterized small animal model that is susceptible to wild-type filoviruses would fac...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
This article argues that researchers should also test the safety and effectiveness of novel vaccines in wild apes by employing a pluralistic approach to evidence. There are three reasons to test vaccines in wild populations of apes: i) protect apes; ii) reduce Ebola transmission from wild animals to humans; and iii) accelerate vaccine development and licensing for humans. Data obtained from studies of vaccines among wild apes and chimpanzees may even be considered sufficient for licensing new vaccines for humans. This strategy will serve to benefit both wild apes and humans. PMID: 30339070 [PubMed - in process]
Source: American Journal of Bioethics - Category: Medical Ethics Tags: Am J Bioeth Source Type: research
Abstract Testing vaccine efficacy against the highly lethal Ebola virus (EBOV) in humans is almost impossible due to obvious ethical reasons and the sporadic nature of outbreaks. For such situations, the 'animal rule' was established, requiring the product be tested in animal models, expected to predict the response observed in humans. For vaccines, this testing aims to identify immune correlates of protection, such as antibody or cell-mediated responses. In the wake of the 2013-2016 EBOV epidemic, and despite advancement of promising candidates into clinical trials, protective correlates remain ambiguous. In the ...
Source: Trends in Microbiology - Category: Microbiology Authors: Tags: Trends Microbiol Source Type: research
In this study, we prepared the extracellular domain of the EBOV GP protein (designated as N20) by prokaryotic expression and purification via chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we evaluated the immunogenicity of N20 by intranasal administration and the associated protective efficacy against mouse-adapted EBOV challenge in mice. We found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on IgG subclasses and IFN-γ/IL-4 secreting cells; and mucosal immunity, based on the presenc...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
The World Health Organization (WHO) has announced the end of the Ebola outbreak in the Democratic Republic of the Congo (DRC)—the country’s ninth outbreak of the deadly virus—after a total of 53 confirmed and probable cases were reported, including 33 deaths. “The outbreak was contained due to the tireless efforts of local teams, the support of partners, the generosity of donors, and the effective leadership of the Ministry of Health. That kind of leadership, allied with strong collaboration between partners, saves lives,” said WHO Director-General, Dr Tedros Adhanom Ghebreyesus in a statemen...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized ebola healthytime onetime Source Type: news
Publication date: Available online 17 March 2018Source: Microbes and InfectionAuthor(s): Sagar B. Kudchodkar, Hyeree Choi, Emma L. Reuschel, Rianne Esquivel, Jackie Jin-Ah Kwon, Moonsup Jeong, Joel N. Maslow, Charles C. Reed, Scott White, J. Joseph Kim, Gary P. Kobinger, Pablo Tebas, David B. Weiner, Kar MuthumaniAbstractVaccines are considered one of the greatest advances in modern medicine. The global burden of numerous infectious diseases has been significantly reduced, and in some cases, effectively eradicated through the deployment of specific vaccines. However, efforts to develop effective new vaccines against infect...
Source: Microbes and Infection - Category: Infectious Diseases Source Type: research
More News: African Health | Cytology | Ebola | Ebola Vaccine | International Medicine & Public Health | Outbreaks | Study | Vaccines | Veterinary Vaccinations