About this item:

121 Views | 122 Downloads

Author Notes:

Tel.: +1-608-265-0666 (E.R.W.); +1-404-712-6604 (L.J.A.); Fax: +1-608-265-4693 (E.R.W.); +1-404-727-9223 (L.J.A.); erwright2@wisc.edu; larry.anderson@emory.edu

B.H., J.E.Y., E.R.W., and L.J.A. participated in conceptualization, validation, formal analysis, investigation, data curation; B.H., E.R.W., and L.J.A. participated in project administration; B.H. wrote the initial draft; B.H., L.J.A., J.E.Y., and E.R.W. participated in data analysis and interpretation. B.H., J.E.Y., X.C., S.J.J., E.R.W., and L.J.A. participated in the methodology, review, and editing; L.J.A. and E.R.W. participated in funding acquisition. All authors have read and agreed to the published version of the manuscript.

The authors gratefully acknowledge use of facilities and instrumentation at the UW-Madison Wisconsin Centers for Nanoscale Technology (wcnt.wisc.edu), which is partially supported by the NSF through the University of Wisconsin Materials Research Science and Engineering Center (DMR-1720415). We would also like to thank the Pathology core lab at Emory University for histological services and support.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was supported in part by Emory University and Children’s Healthcare of Atlanta. L.J.A. receives support from NIH U19 AI 095227 and through the Vaccine and Treatment Evaluation Units (VTEU) award to Emory University (HHSN272201300018I). This work was also supported by the University of Wisconsin, Madison and public health service grant R01 GM114561 to E.R.W. from the NIH.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • respiratory syncytial virus (RSV)
  • virus-like particles (VLPs)
  • vaccine
  • electron microscopy (EM)
  • mouse model
  • RESPIRATORY SYNCYTIAL VIRUS
  • NUCLEOPROTEIN-RNA COMPLEX
  • MONOCLONAL-ANTIBODY
  • FUSION PROTEIN
  • CRYSTAL-STRUCTURE
  • MATRIX PROTEIN
  • YOUNG-CHILDREN
  • INFECTION
  • VACCINE
  • M2-1

Two RSV Platforms for G, F, or G plus F Proteins VLPs

Tools:

Journal Title:

VIRUSES-BASEL

Volume:

Volume 12, Number 9

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

Respiratory syncytial virus (RSV) causes substantial lower respiratory tract disease in children and at-risk adults. Though there are no effective anti-viral drugs for acute disease or licensed vaccines for RSV, palivizumab prophylaxis is available for some high risk infants. To support anti-viral and vaccine development efforts, we developed an RSV virus-like particle (VLP) platform to explore the role RSV F and G protein interactions in disease pathogenesis. Since VLPs are immunogenic and a proven platform for licensed human vaccines, we also considered these VLPs as potential vaccine candidates. We developed two RSV VLP platforms, M+P and M+M2-1 that had F and G, F and a G peptide, or a truncated F and G on their surface. Immunoblots of sucrose gradient purified particles showed co-expression of M, G, and F with both VLP platforms. Electron microscopy imaging and immunogold labeling confirmed VLP-like structures with surface exposed projections consistent with F and G proteins. In mice, the VLPs induced both anti-F and -G protein antibodies and, on challenge, reduced lung viral titer and inflammation. These data show that these RSV VLP platforms provide a tool to study the structure of F and G and their interactions and flexible platforms to develop VLP vaccines in which all components contribute to RSV-specific immune responses.

Copyright information:

© 2020 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote