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Chimeric papillomavirus-like particles expressing a foreign epitope on capsid surface loops
Katharina Slupetzky1, Saeed Shafti-Keramat1, Petra Lenz1
1Laboratory of Viral Oncology, Division of Immunology, Allergy and Infectious Diseases (DIAID)1, and Division of General Dermatology, Department of Dermatology2, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
The Journal of General Virology
|October 17, 2001
Summary
Understanding papillomavirus (PV) neutralization requires studying capsid epitopes. This research identifies key regions on human PV type 16 (HPV-16) and bovine PV type 1 (BPV-1) L1 proteins that are crucial for antibody-mediated immune protection.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Neutralization epitopes on papillomavirus (PV) capsid proteins are critical for antibody-mediated protection against PV infection and disease.
- The L1 major capsid protein forms virus-like particles (VLPs) and pentamers, which are key structures for vaccine development and understanding immune responses.
Purpose of the Study:
- To investigate the role of specific regions within the L1 capsid protein of human PV type 16 (HPV-16) and bovine PV type 1 (BPV-1) in forming neutralization epitopes.
- To assess the impact of incorporating foreign peptides into capsid surface loops on the immunogenicity and VLP assembly.
- To compare the epitope presentation on assembled VLPs versus disassembled pentamers.
Main Methods:
- Construction of chimeric L1 major capsid proteins of HPV-16 and BPV-1 with foreign peptides inserted into surface loops.
- Self-assembly of chimeric proteins into pentamers and virus-like particles (VLPs).
- Binding assays using neutralizing monoclonal antibodies (MAb).
- Immunization of mice to assess immunogenicity.
Main Results:
- Regions around amino acids 282-286 and 351-355 of the L1 protein were identified as contributors to neutralization epitopes.
- The region around aa 351-355 was found to be an immunodominant site.
- Incorporating a foreign peptide into an assembled VLP structure significantly enhanced its immunogenicity.
- Disassembled pentamers from wild-type VLPs retained some neutralization epitopes but lost binding for a subset of neutralizing MAbs that inhibit cell attachment.
Conclusions:
- Specific regions within the PV L1 capsid protein are critical for defining neutralization epitopes and immune protection.
- The structural context of assembled VLPs is important for presenting certain epitopes effectively and enhancing immunogenicity.
- Understanding epitope presentation on both assembled and disassembled viral structures is crucial for developing effective PV vaccines.