Structural engineering of stabilized, expanded epitope nanoparticle vaccines for HPV

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.