Epitopes described in "Cross-neutralization of four paramyxoviruses by a human monoclonal antibody."

Reference
Article Authors:Davide Corti; Siro Bianchi; Fabrizia Vanzetta; Andrea Minola; Laurent Perez; Gloria Agatic; Barbara Guarino; Chiara Silacci; Jessica Marcandalli; Benjamin J Marsland; Antonio Piralla; Elena Percivalle; Federica Sallusto; Fausto Baldanti; Antonio Lanzavecchia
Article Title:Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.
Reference Detail
Reference ID:1026832
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 -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.
Date:2013
Reference Type:Literature
PubMed ID:23955151
Journal:Nature
Journal Volume:501
Article Pages:439-43
Journal ISSN:1476-4687
Article Chemical List:Antibodies, Monoclonal;Antibodies, Neutralizing;Epitopes;Immunoglobulin Light Chains;Immunoglobulin Variable Region;Viral Fusion Proteins;Viral Vaccines
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Monoclonal(chemistry; immunology; isolation & purification; therapeutic use); Antibodies, Neutralizing(chemistry; immunology; isolation & purification; therapeutic use); Antibody Specificity(immunology); Cattle; Cross Reactions(immunology); Epitopes(immunology); Humans; Immunoglobulin Light Chains(chemistry; immunology); Immunoglobulin Variable Region(chemistry; immunology); Metapneumovirus(immunology); Mice; Models, Molecular; Molecular Sequence Data; Murine pneumonia virus(immunology); Paramyxoviridae(classification; immunology); Paramyxoviridae Infections(immunology; prevention & control; therapy; virology); Pneumovirus Infections(immunology; prevention & control; virology); Respiratory Syncytial Virus Infections(immunology; prevention & control; therapy; virology); Respiratory Syncytial Virus, Bovine(immunology); Respiratory Syncytial Virus, Human(immunology); Viral Fusion Proteins(chemistry; immunology); Viral Vaccines(chemistry; immunology)
Curation Last Updated:2014-10-03 23:01:41