The human papillomavirus (HPV) vaccine is a triumph of modern medicine—but it cannot eliminate an existing infection. Once HPV takes hold, no approved vaccines can stop its progression to cervical cancer, leaving surgery and chemotherapy as the main options. Researchers at Chiba University are working to change that with a nanogel nasal vaccine that shows promise in preclinical models.
The study, led by associate professor Rika Nakahashi-Ouchida, MD, and Hiromi Mori of Chiba University Hospital, was published in Science Translational Medicine. The paper, titled “Cationic nanogel–based nasal therapeutic HPV vaccine prevents the development of cervical cancer,” describes a vaccine that activates local immune responses and slows tumor growth in animal models.
Cervical cancer is one of the most common cancers in women worldwide and is primarily caused by persistent infection with high-risk strains of HPV. While prophylactic HPV vaccines can prevent infection, they do not treat existing infections or HPV-associated cancers. “Therapeutic vaccines against cervical cancer caused by human papillomavirus (HPV) are still an unmet medical need,” the authors write. Current treatments—surgery, chemotherapy, and radiotherapy—can be invasive and compromise fertility, underscoring the need for alternatives.
To address this gap, the Chiba University team developed a nasal vaccine using cationic cholesteryl-group-bearing nanogels (cCHP) to deliver HPV antigens directly to the nasal mucosa. These positively charged nanogels adhere to the negatively charged nasal surface, gradually releasing the antigen payload. The vaccine targets the E7 oncoprotein produced by HPV16, a common high-risk strain that inactivates the tumor suppressor pRb and drives cervical cancer progression.
The researchers combined the E7 antigen with cyclic-di-AMP (c-di-AMP), an adjuvant known to enhance T-cell-mediated immunity. This formulation, cCHP-E7 + c-di-AMP, was administered intranasally to mice and macaques. In mice, the vaccine significantly slowed tumor growth and induced E7-specific CD4+ and CD8+ T cells in cervicovaginal tissue. In macaques, four doses delivered via a human-compatible nasal spray device triggered strong immune responses in cervical tissue, including sustained levels of E7-specific killer T cells four months after the final dose.
“We have developed an intranasal therapeutic vaccine as a nonsurgical alternative to conventional treatments that can compromise women’s quality of life,” said Nakahashi-Ouchida. “This novel nasal vaccine activates the mucosal homing pathways of lymphocytes, allowing it to trigger an immune response in the cervical mucosa.”
The findings suggest that nasal delivery can stimulate mucosal immunity in the reproductive tract via the respiratory-reproductive axis—a concept previously demonstrated by the team in herpes simplex virus models. Importantly, the vaccine’s ability to induce local immune responses in primates supports its translational potential.
Cervical cancer remains a pressing global health challenge. According to the World Health Organization, there were around 670,000 new cases and 350,000 deaths worldwide in 2022, making it the fourth most common cancer in women. The burden falls disproportionately on low- and middle-income countries, where access to HPV vaccination, screening, and treatment is limited. These stark numbers underscore the need for therapeutic strategies that go beyond prevention.
As the search for therapeutic options against HPV-driven cancers continues, the Chiba University team’s work highlights how nanogel-based nasal vaccines could reshape the landscape of cervical cancer treatment. By combining local immune activation with a non-invasive delivery method, this approach offers the possibility of preserving fertility and improving quality of life for patients.
“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,” said Nakahashi-Ouchida. While further clinical testing will be essential, the findings mark an important step toward expanding the role of immunotherapy beyond prevention and into treatment, opening the door to a new generation of mucosal-targeted vaccines.
