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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus
Xiaolin Wen1, Jarrod J Mousa2, John T Bates2
1Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
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 burden2-6. 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.
Insights
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause significant illness. Researchers identified cross-reactive antibodies targeting their fusion (F) proteins, offering potential for new vaccines and treatments against these paramyxoviruses.
Area of Science:
- Virology and immunology
- Structural biology
- Vaccine development
Background:
- Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are significant respiratory pathogens, particularly in infants and the elderly.
- Currently, no licensed vaccines or specific antiviral treatments exist for these closely related viruses.
- Understanding cross-immunity and host responses is crucial for developing effective control strategies.
Purpose of the Study:
- To investigate the structural basis of cross-reactive antibody binding to RSV and HMPV fusion (F) proteins.
- To identify conserved regions on the F proteins responsible for cross-reactivity.
- To inform the development of broadly protective vaccines against paramyxoviruses.
Main Methods:
- Structural determination of the MPE8 antibody bound to the RSV F protein.
- Identification of the 25P13 antibody from an independent blood donor.
- Analysis of antibody-F protein interactions, focusing on conserved surfaces and germline residues.
Main Results:
- Two related antibodies, MPE8 and 25P13, bind to conserved surfaces on the RSV and HMPV F proteins.
- Both antibodies utilize germline residues for interaction, suggesting a common mechanism for cross-reactivity.
- The identified conserved surface on the F protein is a key target for cross-reactive neutralizing antibodies.
Conclusions:
- Structural insights reveal how antibodies can achieve cross-reactivity against RSV and HMPV F proteins.
- Targeting conserved F protein epitopes with structurally guided vaccines could induce broad immunity.
- This approach holds promise for enhancing cross-immunity and controlling paramyxovirus outbreaks.
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