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Published on: July 27, 2021
A Chimeric Pneumovirus Fusion Protein Carrying Neutralizing Epitopes of Both MPV and RSV
Xiaolin Wen1, Jennifer Pickens2,3, Jarrod J Mousa2,3
1Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, United States of America.
Abstract:
Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are paramyxoviruses that are responsible for substantial human health burden, particularly in children and the elderly. The fusion (F) glycoproteins are major targets of the neutralizing antibody response and studies have mapped dominant antigenic sites in F. Here we grafted a major neutralizing site of RSV F, recognized by the prophylactic monoclonal antibody palivizumab, onto HMPV F, generating a chimeric protein displaying epitopes of both viruses. We demonstrate that the resulting chimeric protein (RPM-1) is recognized by both anti-RSV and anti-HMPV F neutralizing antibodies indicating that it can be used to map the epitope specificity of antibodies raised against both viruses. Mice immunized with the RPM-1 chimeric antigen generate robust neutralizing antibody responses to MPV but weak or no cross-reactive recognition of RSV F, suggesting that grafting of the single palivizumab epitope stimulates a comparatively limited antibody response. The RPM-1 protein provides a new tool for characterizing the immune responses resulting from RSV and HMPV infections and provides insights into the requirements for developing a chimeric subunit vaccine that could induce robust and balanced immunity to both virus infections.
Insights
Researchers created a chimeric protein (RPM-1) from respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) fusion (F) glycoproteins. This tool helps map antibody responses to both viruses, aiding future vaccine development.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause significant health issues, especially in vulnerable populations.
- The fusion (F) glycoproteins of these viruses are key targets for neutralizing antibodies.
- Understanding antigenic sites on F glycoproteins is crucial for effective vaccine design.
Purpose of the Study:
- To create a chimeric F glycoprotein (RPM-1) displaying epitopes from both RSV and HMPV.
- To evaluate RPM-1 as a tool for mapping the specificity of neutralizing antibodies against RSV and HMPV.
- To assess the immunogenicity of RPM-1 in mice for potential vaccine applications.
Main Methods:
- Grafting a dominant neutralizing epitope from RSV F onto HMPV F to create the chimeric RPM-1 protein.
- Testing RPM-1 recognition by anti-RSV and anti-HMPV neutralizing antibodies.
- Immunizing mice with RPM-1 and analyzing the resulting neutralizing antibody responses against both viruses.
Main Results:
- The chimeric RPM-1 protein was recognized by neutralizing antibodies against both RSV and HMPV F glycoproteins.
- Mice immunized with RPM-1 developed strong neutralizing antibodies against HMPV but weak responses against RSV.
- The single palivizumab epitope graft stimulated a limited cross-reactive antibody response.
Conclusions:
- RPM-1 serves as a valuable tool for characterizing immune responses to RSV and HMPV infections.
- The study provides insights into the challenges of developing a chimeric subunit vaccine for broad protection against both viruses.
- Further research is needed to design chimeric antigens that elicit robust and balanced immunity to both RSV and HMPV.
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