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Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it.

ABSTRACT: The ebolavirus (EBOV) envelope glycoprotein (GP) is solely responsible for viral attachment to, fusion with, and entry of new host cells, and consequently is a major target of vaccine design efforts. Recently determined crystal structures of key antibodies in complex with their EBOV epitopes have provided insights into the molecular architecture of GP and defined likely hotspots for viral neutralization. In this review, we discuss the structural basis for antibody-mediated neutralization of ebolavirus and its implications for novel therapeutic or vaccine strategies.

SUBMITTER: Lee JE

PROVIDER: S-EPMC2759674 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it.

Lee Jeffrey E JE Saphire Erica Ollmann EO

Current opinion in structural biology 20090624 4

The ebolavirus (EBOV) envelope glycoprotein (GP) is solely responsible for viral attachment to, fusion with, and entry of new host cells, and consequently is a major target of vaccine design efforts. Recently determined crystal structures of key antibodies in complex with their EBOV epitopes have provided insights into the molecular architecture of GP and defined likely hotspots for viral neutralization. In this review, we discuss the structural basis for antibody-mediated neutralization of ebol ...[more]

PMID: 19559599

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Project description:Human cytomegalovirus (HCMV) is an important, ubiquitous pathogen that causes severe clinical disease in immunocompromised individuals, such as organ transplant recipients and infants infected in utero. Antiviral chemotherapy remains problematic due to toxicity of the available compounds and the emergence of viruses resistant to available antiviral therapies. Antiviral antibodies could represent a valuable alternative strategy to limit the clinical consequences of viral disease in patients. The envelope glycoprotein B (gB) of HCMV is a major antigen for the induction of virus neutralizing antibodies. However, the role of anti-gB antibodies in the course of the infection in-vivo remains unknown. We have used a murine CMV (MCMV) model to generate and study a number of anti-gB monoclonal antibodies (mAbs) with differing virus-neutralizing capacities. The mAbs were found to bind to similar antigenic structures on MCMV gB that are represented in HCMV gB. When mAbs were used in immunodeficient RAG-/- hosts to limit an ongoing infection we observed a reduction in viral load both with mAbs having potent neutralizing capacity in-vitro as well as mAbs classified as non-neutralizing. In a therapeutic setting, neutralizing mAbs showed a greater capacity to reduce the viral burden compared to non-neutralizing antibodies. Efficacy was correlated with sustained concentration of virus neutralizing mAbs in-vivo rather than their in-vitro neutralizing capacity. Combinations of neutralizing mAbs further augmented the antiviral effect and were found to be as potent in protection as polyvalent serum from immune animals. Prophylactic administration of mAbs before infection was also protective and both neutralizing and non-neutralizing mAbs were equally effective in preventing lethal infection of immunodeficient mice. In summary, our data argue that therapeutic application of potently neutralizing mAbs against gB represent a strategy to modify the outcome of CMV infection in immunodeficient hosts. When present before infection, both neutralizing and non-neutralizing anti-gB exhibited protective capacity.

Dataset Information

Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it.

Publications

Neutralizing ebolavirus: structural insights into the envelope glycoprotein and antibodies targeted against it.

Similar Datasets

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