Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV
Oncogenic forms of HPV account for 4.5% of the global cancer burden worldwide. This includes cervical, vaginal, vulvar, penile, and anal cancers, as well as head and neck cancers. As such, there is an urgent need to develop effective therapeutic vaccines to drive the immune system’s cellular respons...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535261/full |
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| author | Michaela Helble Michaela Helble Xizhou Zhu Pratik S. Bhojnagarwala Kevin Liaw Yangcheng Gao Amber Kim Kelly Bayruns Madison E. McCanna Joyce Park Kylie M. Konrath Kylie M. Konrath Sam Garfinkle Sam Garfinkle Taylor Brysgel David B. Weiner David B. Weiner Daniel W. Kulp Daniel W. Kulp |
| author_facet | Michaela Helble Michaela Helble Xizhou Zhu Pratik S. Bhojnagarwala Kevin Liaw Yangcheng Gao Amber Kim Kelly Bayruns Madison E. McCanna Joyce Park Kylie M. Konrath Kylie M. Konrath Sam Garfinkle Sam Garfinkle Taylor Brysgel David B. Weiner David B. Weiner Daniel W. Kulp Daniel W. Kulp |
| author_sort | Michaela Helble |
| collection | DOAJ |
| description | Oncogenic forms of HPV account for 4.5% of the global cancer burden worldwide. This includes cervical, vaginal, vulvar, penile, and anal cancers, as well as head and neck cancers. As such, there is an urgent need to develop effective therapeutic vaccines to drive the immune system’s cellular response against cancer cells. One of the primary goals of cancer vaccination is to increase the potency and diversity of anti-tumor T-cell responses; one strategy to do so involves the delivery of full-length cancer antigens scaffolded onto DNA-launched nanoparticles to improve T-cell priming. We developed a platform, making use of structural prediction algorithms such as AlphaFold2, to design stabilized, more full-length antigens of relevant HPV proteins and then display them on nanoparticles. We demonstrated that many such designs for both the HPV16 E6 and E7 antigens assembled and drove strong CD8+ T-cell responses in mice. We further tested nanoparticles in a genetically diverse, more translationally relevant CD-1 mouse model and demonstrated that both E6 and E7 nanoparticle designs drove a CD8+ biased T-cell response. These findings serve as a proof-of-concept study for nanoparticle antigen design as well as identify new vaccine candidates for HPV-associated cancers. |
| format | Article |
| id | doaj-art-a3875a4c2aa54b0daf2d56de73a81b4b |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a3875a4c2aa54b0daf2d56de73a81b4b2025-01-31T09:19:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15352611535261Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPVMichaela Helble0Michaela Helble1Xizhou Zhu2Pratik S. Bhojnagarwala3Kevin Liaw4Yangcheng Gao5Amber Kim6Kelly Bayruns7Madison E. McCanna8Joyce Park9Kylie M. Konrath10Kylie M. Konrath11Sam Garfinkle12Sam Garfinkle13Taylor Brysgel14David B. Weiner15David B. Weiner16Daniel W. Kulp17Daniel W. Kulp18The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesThe Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United StatesPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesOncogenic forms of HPV account for 4.5% of the global cancer burden worldwide. This includes cervical, vaginal, vulvar, penile, and anal cancers, as well as head and neck cancers. As such, there is an urgent need to develop effective therapeutic vaccines to drive the immune system’s cellular response against cancer cells. One of the primary goals of cancer vaccination is to increase the potency and diversity of anti-tumor T-cell responses; one strategy to do so involves the delivery of full-length cancer antigens scaffolded onto DNA-launched nanoparticles to improve T-cell priming. We developed a platform, making use of structural prediction algorithms such as AlphaFold2, to design stabilized, more full-length antigens of relevant HPV proteins and then display them on nanoparticles. We demonstrated that many such designs for both the HPV16 E6 and E7 antigens assembled and drove strong CD8+ T-cell responses in mice. We further tested nanoparticles in a genetically diverse, more translationally relevant CD-1 mouse model and demonstrated that both E6 and E7 nanoparticle designs drove a CD8+ biased T-cell response. These findings serve as a proof-of-concept study for nanoparticle antigen design as well as identify new vaccine candidates for HPV-associated cancers.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535261/fullAIAlphaFoldMHC-restrictionCTLHPVnanoparticle |
| spellingShingle | Michaela Helble Michaela Helble Xizhou Zhu Pratik S. Bhojnagarwala Kevin Liaw Yangcheng Gao Amber Kim Kelly Bayruns Madison E. McCanna Joyce Park Kylie M. Konrath Kylie M. Konrath Sam Garfinkle Sam Garfinkle Taylor Brysgel David B. Weiner David B. Weiner Daniel W. Kulp Daniel W. Kulp Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV Frontiers in Immunology AI AlphaFold MHC-restriction CTL HPV nanoparticle |
| title | Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV |
| title_full | Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV |
| title_fullStr | Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV |
| title_full_unstemmed | Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV |
| title_short | Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV |
| title_sort | structural engineering of stabilized expanded epitope nanoparticle vaccines for hpv |
| topic | AI AlphaFold MHC-restriction CTL HPV nanoparticle |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1535261/full |
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