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

Wen, Xiaolin; Mousa, Jarrod J.; Bates, John T.; Lamb, Robert A.; Crowe, James E.; Jardetzky, Theodore S.

doi:10.1038/nmicrobiol.2016.272

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

Journal Article · Mon Jan 30 00:00:00 EST 2017 · Nature Microbiology

DOI:https://doi.org/10.1038/nmicrobiol.2016.272· OSTI ID:1438923

Wen, Xiaolin ^[1]; Mousa, Jarrod J. ^[2];

^[2]; Lamb, Robert A. ^[3]; Crowe, James E. ^[2]; Jardetzky, Theodore S. ^[1]

Stanford Univ., CA (United States)
Vanderbilt Univ., Nashville, TN (United States)
Northwestern Univ., Evanston, IL (United States)

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two closely related viruses that cause bronchiolitis and pneumonia in infants and the elderly1, with a significant health burden2–6. 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 infection7,8, 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 outbreaks9, 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 identified10,11. 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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: GM-61050; AI-23173

OSTI ID:: 1438923

Journal Information:: Nature Microbiology, Vol. 2, Issue 4; ISSN 2058-5276

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 53 works

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