Letter | Published:

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

Nature Microbiology volume 2, Article number: 16272 (2017) | Download Citation

Abstract

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,​3,​4,​5,​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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Acknowledgements

The authors acknowledge support from the members of the Jardetzky, Lamb and Crowe laboratories. This research was supported in part by National Institutes of Health research grants AI-23173 (to R.A.L.) and GM-61050 (to T.S.J.). R.A.L. is an Investigator of the Howard Hughes Medical Institute.

Author information

Affiliations

  1. Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Xiaolin Wen
    •  & Theodore S. Jardetzky
  2. Vanderbilt Vaccine Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA

    • Jarrod J. Mousa
    • , John T. Bates
    •  & James E. Crowe Jr
  3. Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208-3500, USA

    • Robert A. Lamb
  4. Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208-3500, USA

    • Robert A. Lamb
  5. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA

    • James E. Crowe Jr
  6. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA

    • James E. Crowe Jr

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Contributions

X.W., J.J.M., J.T.B., R.A.L., J.E.C. and T.S.J. conceived and designed the experiments. X.W., J.J.M. and J.T.B. performed the experiments. X.W., J.J.M., J.T.B., R.A.L., J.E.C. and T.S.J. analysed the data. X.W., J.J.M. and J.T.B. contributed reagents, materials and analysis tools. X.W., J.J.M., J.T.B., R.A.L., J.E.C. and T.S.J. wrote and edited the manuscript.

Competing interests

One of the authors (J.E.C.) declares a competing interest. J.E.C. is a consultant to Compuvax and a member of the Scientific Advisory Board of Meissa Vaccines. The remaining authors declare no competing interests.

Corresponding author

Correspondence to Theodore S. Jardetzky.

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    Supplementary Information

    Supplementary Figures 1–7; Supplementary Tables 1 and 2; Supplementary References.

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DOI

https://doi.org/10.1038/nmicrobiol.2016.272

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