Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus.

Wen X, Mousa JJ, Bates JT, Lamb RA, Crowe JE, Jardetzky TS
Nat Microbiol. 2017 2: 16272

PMID: 28134915 · PMCID: PMC5308794 · DOI:10.1038/nmicrobiol.2016.272

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two closely related viruses that cause bronchiolitis and pneumonia in infants and the elderly, with a significant health burden. There are no licensed vaccines or small-molecule antiviral treatments specific to these two viruses at present. A humanized murine monoclonal antibody (palivizumab) is approved to treat high-risk infants for RSV infection, but other treatments, as well as vaccines, for both viruses are still in development. Recent epidemiological modelling suggests that cross-immunity between RSV, HMPV and human parainfluenzaviruses may contribute to their periodic outbreaks, suggesting that a deeper understanding of host immunity to these viruses may lead to enhanced strategies for their control. Cross-reactive neutralizing antibodies to the RSV and HMPV fusion (F) proteins have been identified. Here, we examine the structural basis for cross-reactive antibody binding to RSV and HMPV F protein by two related, independently isolated antibodies, MPE8 and 25P13. We solved the structure of the MPE8 antibody bound to RSV F protein and identified the 25P13 antibody from an independent blood donor. Our results indicate that both antibodies use germline residues to interact with a conserved surface on F protein that could guide the emergence of cross-reactivity. The induction of similar cross-reactive neutralizing antibodies using structural vaccinology approaches could enhance intrinsic cross-immunity to these paramyxoviruses and approaches to controlling recurring outbreaks.

MeSH Terms (11)

Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Cross Reactions Crystallography, X-Ray Metapneumovirus Models, Molecular Protein Binding Protein Conformation Respiratory Syncytial Viruses Viral Fusion Proteins

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