Researchers at Chiba University have made significant strides in the fight against cervical cancer by developing an innovative intranasal vaccine. This therapeutic approach aims to address the limitations of existing HPV vaccines, which cannot treat pre-existing infections or HPV-related cancers. The study, led by Associate Professor Rika Nakahashi-Ouchida and Hiromi Mori, was published in the journal Science Translational Medicine.
Cervical cancer, primarily caused by persistent infections with high-risk strains of human papillomavirus (HPV), remains a pressing global health issue. According to the World Health Organization, there were approximately 670,000 new cases and 350,000 deaths worldwide in 2022, making it the fourth most common cancer among women. The majority of these cases occur in low- and middle-income countries where access to vaccination, screening, and treatment options is often limited.
The research team at Chiba University has created a nasal vaccine using cationic cholesteryl-group-bearing nanogels (cCHP), which deliver HPV antigens directly to the nasal mucosa. This method allows the vaccine to activate local immune responses effectively. The formulation combines the E7 oncoprotein, produced by HPV16, with cyclic-di-AMP (c-di-AMP), an adjuvant known to enhance T-cell-mediated immunity.
In preclinical trials, administering the vaccine intranasally to mice resulted in a significant slowdown of tumor growth and the induction of E7-specific CD4+ and CD8+ T cells in cervicovaginal tissue. Further testing on macaques demonstrated that four doses delivered through a human-compatible nasal spray device triggered robust immune responses, including sustained levels of E7-specific killer T cells even four months after the final dose.
Nakahashi-Ouchida emphasized the potential of this intranasal vaccine as a nonsurgical alternative to conventional treatments, which can significantly impact women’s quality of life. “This novel nasal vaccine activates the mucosal homing pathways of lymphocytes, allowing it to trigger an immune response in the cervical mucosa,” she stated.
The findings indicate that nasal delivery may stimulate mucosal immunity in the reproductive tract via the respiratory-reproductive axis, a concept previously validated in models involving herpes simplex virus. The ability of the vaccine to elicit local immune responses in primates supports its potential for future clinical applications.
As the search for effective therapeutic options for HPV-driven cancers continues, the work from Chiba University highlights the promise of nanogel-based nasal vaccines. This innovative approach not only combines local immune activation with a non-invasive delivery method but also offers the potential to preserve fertility and improve patient quality of life.
Nakahashi-Ouchida added, “Immunotherapies such as intranasal therapeutic vaccines may help establish a new category of noninvasive treatment. These approaches could be extended to recurrence prevention and chronic disease management, offering patients safer and more accessible options.”
While further clinical testing is necessary, this research marks a crucial advancement in the expansion of immunotherapy beyond prevention, paving the way for a new generation of targeted mucosal vaccines.
