Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.

Details

Serval ID
serval:BIB_95FA5E5EA73A
Type
Article: article from journal or magazin.
Publication sub-type
Letter (letter): Communication to the publisher.
Collection
Publications
Institution
Title
Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.
Journal
Nature
Author(s)
Corti D., Bianchi S., Vanzetta F., Minola A., Perez L., Agatic G., Guarino B., Silacci C., Marcandalli J., Marsland B.J., Piralla A., Percivalle E., Sallusto F., Baldanti F., Lanzavecchia A.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
2013
Volume
501
Number
7467
Pages
439-443
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and HIV-1 (ref. 1). However, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma exacerbations. Although antisera generated against either HRSV or HMPV are not cross-neutralizing, we speculated that, because of the repeated exposure to these viruses, cross-neutralizing antibodies may be selected in some individuals. Here we describe a human monoclonal antibody (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its germline configuration, MPE8 is HRSV-specific and its breadth is achieved by somatic mutations in the light chain variable region. MPE8 did not result in the selection of viral escape mutants that evaded antibody targeting and showed potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM infection. The core epitope of MPE8 was mapped on two highly conserved anti-parallel β-strands on the pre-fusion viral F protein, which are rearranged in the post-fusion F protein conformation. Twenty-six out of the thirty HRSV-specific neutralizing antibodies isolated were also found to be specific for the pre-fusion F protein. Taken together, these results indicate that MPE8 might be used for the prophylaxis and therapy of severe HRSV and HMPV infections and identify the pre-fusion F protein as a candidate HRSV vaccine.
Pubmed
Web of science
Create date
17/10/2013 16:33
Last modification date
20/08/2019 14:58
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