Prima touts human trials hopes for vaccine tech

Prima Biomed subsidiary PanVax is planning to test its DCtag adjuvant technology with an existing marketed vaccine in human clinical trials, aiming to demonstrate enhanced immunogenicity of the re-engineered vaccine compared to existing formulations.

CEO Marcus Clark said today the company hoped to announce details of a collaborative agreement with a vaccine manufacturer before the end of the year.

The company also plans to move forward with development of a cancer vaccine against human recombinant colon cancer antigen, carcinoembryonic antigen (rhCEA), a well-studied antigen found in a number of different cancers, and will seek licenses for further oncology applications and for development of a malaria vaccine.

DCtag is a nanoparticle that has been shown by PanVax researchers at the Austin Research Institute to have strong adjuvant, or immune-stimulating, properties when conjugated to antigens. According to Prof Magdalena Plebanski, lead scientist on the project, protective effects are achieved after a single injection.

In addition, DCtag is unique in that it generates both an antibody response and a cellular response. Other adjuvants and strategies such as alum (a common adjuvant) or prime-boost strategies tend to preferentially target one or other arm of the immune response, she said.

"At least in animals, it appears to be more powerful than anything else being tested," Plebanski said. "It's simple, it's stable, it induces long-lasting immunity -- it's so flexible."

The researchers have used a variety of antigens to study the adjuvant's properties, including cancer antigens, malaria antigens, and respiratory virus antigens, and strong immune responses have been generated in mice in each case.

Previously the researchers had shown that a malaria vaccine in combination with DCtag was able to eradicate the malaria infection from the blood of infected mice. Similarly, a DCtag cancer vaccine caused eradication of established tumours in mice.

The adjuvant also has an excellent safety profile, according to Plebanski. In independent toxicology studies in mice no tissue or organ pathology or inflammatory reactions at the site of injection have been observed, clearing the way for human clinical trials. Similar results have been observed in sheep.

The researchers have also made strides in determining the mechanism of action for the adjuvant. "It appears that size matters -- the immune system seems to be preconditioned for taking up and processing antigens and proteins conjugated to particles of a specific size and shape," Plebanski said. The DCtag vaccines appear to be preferentially taken up by a specific subset of dendritic cells, the main cells involved in presenting antigens to the immune system.

Clark said that on the basis of the results the company was moving into the next stage of pre-clinical and clinical development, focusing on viral vaccines, cancer and malaria in particular.

"All these features add up to make a very attractive profile for a vaccine adjuvant. As there are many vaccines providing sub-optimal preventative cover in infectious diseases we see a significant opportunity and will now be targeting existing vaccines with a view to enhancing their efficacy," said Clark.

Clark said that the company hoped to be able to do pre-clinical studies and begin clinical trials on an existing viral vaccine in the first half of next year, contingent on signing on a suitable partner. PanVax is also evaluating potential sources of GMP-quality material.

In addition, the company will move forward with the development of the rhCEA cancer vaccine, with an eye to initiating clinical trials next year. License discussions with the collaboration partners on the project are in progress, according to Clark.

PanVax is also planning to reopen discussions with the WHO-funded Malaria Vaccine Initiative, now that toxicology data is available. Clark said that the company would most likely enter a licensing arrangement to continue to the development of the project.

Other collaborations include a project to develop an Alzheimer's vaccine with Prana Biotechnology and a veterinary foot and mouth disease vaccine program supported by the Australian government.