this exclusively prophylactic vaccine has already proven to be safe in phase I clinical trials and induces protective antibodies against all cancer-causing HPV as well as against some cutaneous papillomaviruses.

For PANHPVAX, the researchers used small fragments of the L2 protein from eight different HPV types.

These fragments differ only slightly between different HPV types and can therefore trigger a very broad immune response.

To make these protein snippets immunogenic, they were inserted into a suitable scaffold protein derived from a heat-loving microorganism (Pyrococcus furiosus).

'In our current work, we have added a therapeutic component to PANHPVAX, i.

e.

, an antigen that stimulates the cellular immune response,' explains Müller.

The DKFZ virologists chose the protein E7 of the two high-risk types HPV16 and 18.

It is formed very early in the course of an HPV infection in the infected cells and is therefore an ideal target for a cellular immune response to eliminate these cells.

However, E7 is also responsible for the malignant transformation of HPV-infected cells.

The researchers therefore first had to modify the vaccine antigen so that it no longer posed a threat.

In preclinical studies, the new vaccine cPANHPVAX was able to trigger neutralizing antibodies against all carcinogenic HPV in mice and simultaneously activate cytotoxic T cells against the HPV16 protein E7.

These positive results encouraged the researchers to now produce cPANHPVAX under conditions that comply with Good Manufacturing Practice (GMP) guidelines for pharmaceuticals.

The vaccine produced in this way can be used in clinical trials.

'Our major goal is to increase vaccination rates against HPV worldwide, especially in countries with limited resources.

Our new, heat-stable vaccine is inexpensive to produce, protects against all cancer-causing HPV types, and can potentially neutralize existing infections by combining it with E7.

' In order to further investigate the promising properties of cPANHPVAX, the researchers are currently developing a concept for clinical testing of the vaccine.