title: Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.
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.
authors: Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland. davide.corti@humabs.ch
authors: Davide
authors: D
authors: Corti
authors: Siro
authors: S
authors: Bianchi
authors: Fabrizia
authors: F
authors: Vanzetta
authors: Andrea
authors: A
authors: Minola
authors: Laurent
authors: L
authors: Perez
authors: Gloria
authors: G
authors: Agatic
authors: Barbara
authors: B
authors: Guarino
authors: Chiara
authors: C
authors: Silacci
authors: Jessica
authors: J
authors: Marcandalli
authors: Benjamin J
authors: BJ
authors: Marsland
authors: Antonio
authors: A
authors: Piralla
authors: Elena
authors: E
authors: Percivalle
authors: Federica
authors: F
authors: Sallusto
authors: Fausto
authors: F
authors: Baldanti
authors: Antonio
authors: A
authors: Lanzavecchia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use; D000918:Antibody Specificity / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology; D029121:Metapneumovirus / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D029122:Murine pneumonia virus / Q000276:immunology; D010252:Paramyxoviridae / Q000145:classification* / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy / Q000821:virology*; D018186:Pneumovirus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control / Q000628:therapy / Q000821:virology; D018112:Respiratory Syncytial Virus, Bovine / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D014760:Viral Fusion Proteins; D014765:Viral Vaccines
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