Self-Adjuvanting Peptide Vaccines Against Cervical Cancer

Abstract

Background
Cervical cancer is a common cause of cancer-related deaths in women worldwide, with a fatality rate second only to breast cancer.
Human papillomaviruses (HPVs) are the main causative agents of cervical cancer, and are therefore obvious targets for vaccine
development. Although two prophylactic HPV vaccines have been commercialized, therapeutic vaccines against HPVs have not
been developed yet. Current vaccine technologies emphasize the power of small particles in targeting immune cells, and particles
of 20-50 nm have been reported to induce optimal immune responses against a variety of pathogens and cancers.
Methods
We synthesized new nanoparticle-based vaccines against cervical cancer by using antigenic 8Qmin peptide epitope derived from
HPV-16 E7 protein, a hydrophilic poly-(L-glutamic acid) (PGA) linker, and an 8-arm poly (tert-butyl acrylate) dendrimer-based
delivery system (D8).
Results
Four different peptides containing 8Qmin and PGA of different lengths were successfully synthesized with high yield and purity.
These were then conjugated to alkyne-functionalized D8 by copper-catalyzed alkyne-azide cycloaddition “click” reaction. The
conjugates self-assembled into nanoparticles, with decreased particle size corresponding to a greater number of Glu units. The
four vaccine candidates were tested in C57 black 6 (C57BL/6) mice bearing well-established (7-day-old) tumors to examine their
therapeutic effects.
Conclusion
Interestingly, only one conjugate delayed tumor growth, and montanide adjuvanted antigen, used as a positive control, failed to
demonstrate any therapeutic effect.