A team of researchers at Chiba University has developed a novel intranasal nanogel vaccine that shows potential in treating cervical cancer, a disease primarily caused by persistent infection with high-risk strains of human papillomavirus (HPV). This groundbreaking work, led by Rika Nakahashi-Ouchida, MD, and Hiromi Mori of Chiba University Hospital, was published in the journal Science Translational Medicine.
The study, titled “Cationic nanogel–based nasal therapeutic HPV vaccine prevents the development of cervical cancer,” outlines a vaccine that activates local immune responses and inhibits tumor growth in preclinical animal models. Current HPV vaccines effectively prevent infection but do not address existing infections or HPV-related cancers, making this research a significant advancement in the field.
Cervical cancer remains a pressing global health issue, with around 670,000 new cases and 350,000 deaths reported worldwide in 2022, according to the World Health Organization. The burden of this disease is particularly severe in low- and middle-income countries, where access to effective vaccination, screening, and treatment is limited. The need for therapeutic options that extend beyond prevention is more urgent than ever.
To tackle this pressing medical need, the Chiba University team created a nasal vaccine utilizing cationic cholesteryl-group-bearing nanogels (cCHP) to deliver HPV antigens directly to the nasal mucosa. These positively charged nanogels adhere effectively to the negatively charged nasal surface, gradually releasing their antigen payload. Specifically, the vaccine targets the E7 oncoprotein produced by the high-risk HPV16 strain, which disrupts the function of the tumor suppressor pRb, facilitating the progression of cervical cancer.
The researchers combined the E7 antigen with cyclic-di-AMP (c-di-AMP), an adjuvant recognized for enhancing T-cell-mediated immunity. This formulation, referred to as cCHP-E7 + c-di-AMP, was administered intranasally to both mice and macaques. The results indicated that the vaccine significantly reduced tumor growth in mice and induced E7-specific CD4+ and CD8+ T cells in cervicovaginal tissue. In macaques, four doses delivered via a human-compatible nasal spray device prompted robust immune responses in cervical tissue, including sustained levels of E7-specific killer T cells observed 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,” stated 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 of this research suggest that nasal delivery can effectively stimulate mucosal immunity in the reproductive tract through the respiratory-reproductive axis. This concept has been previously demonstrated by the team in models of herpes simplex virus, reinforcing the translational potential of their approach.
As the medical community continues to seek therapeutic options for HPV-driven cancers, the work done by the Chiba University team highlights the potential of nanogel-based nasal vaccines to transform cervical cancer treatment. By combining local immune activation with a non-invasive delivery method, this strategy may offer patients the chance to preserve fertility and improve their quality of life.
“Immunotherapies such as intranasal therapeutic vaccines may help establish a new category of noninvasive treatment,” Nakahashi-Ouchida added. “These approaches could be extended to recurrence prevention and chronic disease management, providing patients with safer and more accessible options.”
While further clinical trials will be necessary to validate these findings, this research represents a critical step towards expanding the role of immunotherapy beyond prevention to treatment, paving the way for a new generation of mucosal-targeted vaccines.
