A new vaccine aimed at combating cancer-causing human papillomaviruses (HPV) is being developed to enhance vaccination rates, especially in underdeveloped nations. Researchers at the German Cancer Research Center (DKFZ) have introduced a groundbreaking vaccination approach. This vaccine is affordable and has shown effectiveness in mice against nearly all cancer-associated HPV variants. Beyond preventing future infections, it also stimulates immune responses against cells already infected with HPV, suggesting a potential therapeutic benefit for those with existing infections.
new vaccine targeting cancer-causing human papillomaviruses (HPV) is designed to boost HPV vaccination rates, especially in developing regions. Scientists at the German Cancer Research Center (DKFZ) have crafted an innovative vaccination strategy for this aim. This economical vaccine protects mice from nearly all HPV types linked to cancer. Aside from preventing new infections, it provokes immune responses against cells infected by HPV, which may offer therapeutic advantages for current infections.
Certain HPV types lead to cervical cancer, which is the fourth most prevalent cancer among women globally. Most cases are found in less developed regions, particularly in Southeast Asia, Africa, and Latin America. These cancer-causing HPV types are primarily spread through sexual contact, and infections are quite common; it is estimated that around 80 percent of individuals will encounter these viruses at some point in their lives. Besides cervical cancer, high-risk HPV infections are also linked to cancers of the mouth, anus, and other genital areas.
The existing vaccines against cancer-causing HPV are effective but have certain drawbacks. They require refrigeration during transportation, which can be a major logistical challenge in some nations. Their production is not only complex but also costly, and they are only effective against a limited number of HPV types. Most importantly, the current vaccines do not treat existing infections.
In creating their new HPV vaccine, Müller and his team systematically addressed these challenges. They built on a prior model, PANHPVAX, developed in Müller’s lab, which is a fully prophylactic vaccine that has already demonstrated safety in phase I clinical trials and induces protective antibodies against all cancer-causing HPV types, as well as some skin-related papillomaviruses.
The PANHPVAX vaccine utilized small pieces of the L2 protein from eight HPV types. These fragments are slightly different across types but are capable of launching a broad immune response. To enhance their immunogenicity, the team incorporated these protein segments into a suitable scaffold derived from a heat-loving microorganism (Pyrococcus furiosus).
“In our latest research, we added a therapeutic element to PANHPVAX, specifically an antigen that boosts the cellular immune response,” Müller explains. The virologists selected the E7 protein from the high-risk HPV types 16 and 18 for this purpose. This protein is produced early in an HPV infection within infected cells, making it a prime target for the immune system to clear these cells. However, since E7 is responsible for the malignant transformation of infected cells, the researchers needed to modify the vaccine antigen to eliminate any associated risks.
In preclinical trials, the new cPANHPVAX vaccine succeeded in generating neutralizing antibodies against all cancer-causing HPV types in mice, while also activating cytotoxic T cells that target the HPV16 E7 protein.
These promising findings prompted the researchers to produce cPANHPVAX under Good Manufacturing Practice (GMP) conditions for pharmaceuticals, which will enable its use in clinical trials.
“Our primary objective is to enhance HPV vaccination rates worldwide, especially in resource-limited countries. Our new, heat-stable vaccine is inexpensive to produce, protects against all cancer-associated HPV types, and can potentially combat existing infections through the combination with E7.” The team is now developing a plan for clinical trials to further explore the potential of cPANHPVAX.
This research on PANHPVAX and cPANHPVAX was supported by the Wilhelm Sander Foundation.
