Related Experiment Video
Updated: May 27, 2025
Production of E. coli-expressed Self-Assembling Protein Nanoparticles for Vaccines Requiring Trimeric Epitope Presentation
Published on: August 21, 2019
Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV
Michaela Helble1,2, Xizhou Zhu1, Pratik S Bhojnagarwala1
1The Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA, United States.
Abstract:
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.
Insights
Novel nanoparticle vaccines displaying full-length human papillomavirus (HPV) antigens show promise for treating HPV-associated cancers. These vaccines effectively prime CD8+ T-cell responses, crucial for fighting tumors.
Area of Science:
- Immunology
- Vaccinology
- Oncology
- Nanotechnology
Background:
- Human papillomavirus (HPV) causes a significant portion of global cancers, including cervical, anal, and head and neck cancers.
- Developing effective therapeutic vaccines is crucial to enhance cellular immune responses against HPV-driven tumors.
- Current strategies aim to improve T-cell responses, but challenges remain in antigen presentation and vaccine potency.
Purpose of the Study:
- To design and develop stabilized, full-length HPV antigens displayed on nanoparticles for enhanced T-cell priming.
- To evaluate the immunogenicity and efficacy of these novel nanoparticle-based vaccine candidates in preclinical models.
- To establish a platform for designing nanoparticle-displayed antigens using advanced computational tools.
Main Methods:
- Utilized structural prediction algorithms like AlphaFold2 to design stabilized, full-length HPV16 E6 and E7 antigens.
- Scaffolded designed antigens onto DNA-launched nanoparticles for improved antigen delivery and presentation.
- Assessed T-cell responses, specifically CD8+ T-cell responses, in mouse models (including CD-1 mice) following vaccination.
Main Results:
- Multiple designed HPV16 E6 and E7 antigens successfully assembled on nanoparticles.
- Vaccination with these nanoparticle constructs induced strong CD8+ T-cell responses in mice.
- The nanoparticle designs demonstrated a CD8+ biased T-cell response in a genetically diverse mouse model.
Conclusions:
- The study provides proof-of-concept for nanoparticle-based antigen design in vaccine development.
- The developed HPV antigen nanoparticles represent promising vaccine candidates for HPV-associated cancers.
- This platform offers a novel approach to enhance anti-tumor T-cell immunity.
