2016 is looking to be an important year for Admedus as our immunotherapy programs continue to progress well. Working with Professor Ian Frazer and his team, we are developing therapeutic vaccines to target human papillomavirus (HPV) and herpes simplex virus 2 (HSV-2). These vaccines address significant diseases with a huge unmet medical need and if successful, will positively impact patient lives. With this in mind, we wanted to shed some light on how our therapeutic vaccine works to target HPV related tumours and explain the science behind DNA vaccines. For more information on our work to date in targeting HSV-2, please read our previous blog ‘World Health Organisation: You probably have herpes’.

DNA Vaccines & HPV

What are DNA vaccines?

A DNA vaccine is used to stimulate humoral (antibody) and/or cellular (T-cell) immune responses to protein antigens (a foreign material that induces an immune response). This is done by delivering engineered DNA into the body so that a person’s own cells directly express an antigen. The immune system will then target this antigen, thus resulting in a protective immunological response and activated immunity.

Admedus is currently using DNA vaccine technology to develop therapeutic vaccines targeting human papillomavirus (HPV) and herpes simplex virus 2 (HSV-2), although the technology developed by Admedus in conjunction with Professor Ian Frazer can potentially be applied to a range of viruses, bacterial infections and cancers.

What is Human Papillomavirus (HPV)?

According to the Centers for Disease Control and Prevention, HPV is the most common sexually transmitted infection (STI). HPV is so common that nearly all sexually active men and women get it at some point in their lives.

HPV is associated with a number of cancers including cervical cancer and cancer of the vulva, vagina, penis, and rectal cancer. It can also cause cancer in the back of the throat, including the base of the tongue and tonsils (called oropharyngeal cancer), which is also associated with some head and neck cancers.

Cancer often takes years, even decades, to develop after a person is infected with HPV. The types of HPV that can cause genital warts are not the same as the types of HPV that can cause cancers.

HPV can remain asymptomatic and sometimes there is no way to know which people who have HPV will develop cancer or other health problems. People with weak immune systems (including individuals with HIV/AIDS) may be less able to fight off HPV and therefore could be more susceptible to develop health problems related to HPV.

How does Admedus’ DNA vaccine technology work to target HPV?

Using the principles of DNA vaccine technology, we optimise the HPV gene that makes the antigen and transfer it into agency approved DNA plasmids in order to manufacture large amounts of clean, safe and high quality DNA vaccine. This purified DNA vaccine is injected as a solution just under the skin surface (an area which has a high population of migrating immune cells). The plasmid is then taken up by the cells.

Once the vaccine enters into the cells, the cells themselves begin to make a small amount of the foreign antigen which in turn alerts the body’s immune cells to its presence. The Admedus technology adds ubiquitin to the antigen and this helps to flag to the immune system that there is a foreign antigen present. The activated immune system is now on the lookout for anything resembling the foreign antigen, targeting the antigen and anything attached to it and clears it from the body.

Why can’t the body just mount its own defence against HPV?

It’s important to note that not everyone who becomes infected with HPV will have it progress to cancer. Sometimes the body is able to recognise the defective cells and mount its own defence. However, for those people where the HPV infection progresses to the early stages of cancer, Admedus is looking to replicate the process by using its DNA vaccines to produce safe (non-cancer causing) versions of the cancer related proteins in greater numbers and this will train the body into thinking there is a higher level of infected cells, effectively amplifying the immune system and assisting them to mount a better defence.

Is the Admedus vaccine the same as Gardasil?

No. Even though our technology and Gardasil are both created by Professor Ian Frazer, they are very different vaccines. Gardasil creates a prophylactic (antibody) response to protect you from HPV infection in the future. Admedus, on the other hand, is working on a DNA vaccine designed to target and clear HPV-positive tumour cells in people already infected, although the preclinical data indicates it may also work in boosting the immune system in uninfected people.

Why did Admedus invest in the medical technology?

In the US about 79 million people are currently infected with HPV and each year another 14 million people are infected. Whilst Gardasil is a very effective vaccine, the current uptake is quite low, around 40%, and therefore the level of protection from HPV in the community is suboptimal. We feel there is an opportunity to work on a therapeutic vaccine to treat people infected with HPV and with HPV related cancers.

What is the progress of Admedus’ HPV therapeutic vaccine to date?

To date we have completed a number of successful pre-clinical studies with very exciting responses. In a model that replicates the HPV related cancer disease state, treatment with the Admedus HPV vaccine achieved 100% survival after 50 days, and over 85% had no detectable tumours after 50 days. This is a significant advance on published results.

What are the next steps for the vaccine?

Admedus is on track to initiate the first clinical study with the HPV vaccine after the successfully completed pre-clinical studies. As part of this study we will look at safety of the vaccine as well as efficacy data in the study participants.

Therapeutic vaccines, like those being developed by Admedus, typically have shorter clinical studies with fewer participants. This is due to the fact we are looking at a more immediate response in the study participants. Prophylactic vaccines, on the other hand, can take longer as they need to look at differences in large populations of people over a longer period of time. With this in mind, we hope to be able to finalise our study in the next few years.

If you are interested in learning more about our work in HPV, please contact us via the website.

David Rhodes

Chief Scientific Officer