Details

Autor(en) / Beteiligte

• Corti, Davide
• Bianchi, Siro
• Vanzetta, Fabrizia
• Minola, Andrea
• Perez, Laurent
• Agatic, Gloria
• Guarino, Barbara
• Silacci, Chiara
• Marcandalli, Jessica
• Marsland, Benjamin J.
• Piralla, Antonio
• Percivalle, Elena
• Sallusto, Federica
• Baldanti, Fausto
• Lanzavecchia, Antonio

Titel

Cross-neutralization of four paramyxoviruses by a human monoclonal antibody

Ist Teil von

• Nature (London), 2013-09, Vol.501 (7467), p.439-443

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2013

Quelle

EBSCO Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• A human monoclonal antibody has been identified which can cross-neutralize both human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), demonstrating that a single monoclonal antibody can target different viruses, a discovery that may lead to the creation of new therapeutics and vaccines. A broadly active anti-paramyxovirus antibody Human respiratory syncytial virus (HRSV) is a major cause of morbidity and mortality in young children and the elderly, with no effective therapy or vaccine. Corti et al . describe a human monoclonal antibody, named MPE8, with prophylactic and therapeutic potential. The antibody potently cross-neutralizes HRSV and human metapneumovirus, as well as two animal viruses. It is specific for the pre-fusion F protein, suggesting that a vaccine based on a stabilized pre-fusion F protein might be able to selectively elicit neutralizing antibodies. 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 2 , 3 and immune-compromised patients 2 , 4 , 5 , and play a role in asthma exacerbations 6 . Although antisera generated against either HRSV or HMPV are not cross-neutralizing 7 , 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.