Science Editor

Though efforts directed at a vaccine began basically as soon as HIV was identified in 1985, to date few vaccine candidates have even made it into clinical trials, and none of them have been successful.

Indeed, at the recent meeting of the American Association for the Advancement of Science, David Baltimore, AAAS president, told the audience that "There is no AIDS vaccine and no hopeful candidate vaccine." (See BioWorld Today, Feb. 15, 2008.)

The virus has several features that make it a tougher than average candidate to develop a vaccine for, including the fact that it mutates rapidly, attacks the immune system directly and spends much of its life cycle intracellularly.

But executives at the International Aids Vaccine Initiative, or IAVI, believe that an AIDS vaccine is possible. Scientific studies show that "broadly neutralizing antibodies exist," IAVI President Seth Berkley told BioWorld Today. The challenge is to find the antigens that will elicit them in the form of a vaccine. "Antibodies are the lock, and we are looking for the keys."

To find those keys, though, the locksmiths will have to get a move on.

"With small molecules, most of [drug discovery] is now done high-throughput," Berkley said. "That hasn't been the case with biologics."

The way antigen discovery for vaccines works is at least intrinsically logical, explained Wayne Koff, IAVI senior vice president of research and development. "A lab scientist . . . can make a couple of antigens a month. And at this rate, we are able to screen these antigens in the rabbit model" - the preclinical animal model used to test many vaccines, he said.

That model, however, is slow, expensive and not necessarily a good predictor of human responses.

IAVI wants to change that, in part, through a new fund aimed at financing early stage technologies that currently are not being used in AIDS research, but could be useful in the search for a successful vaccine candidate.

The goal of the innovation fund is to "take technologies forward that haven't been proven in the HIV space, but could potentially result in a breakthrough for AIDS vaccines" through seed funding, Berkley said.

IAVI already has collaborations with several academic institutions, as well as the Indian government to increase the number of potential promising antigens for an HIV vaccine. If and when those efforts bear fruit, there will need to be a faster way to screen those antigens.

That's where VaxDesign comes in.

The Orlando, Fl.-based company, which was founded in 2003 and has about 35 employees, essentially is engineering the human immune system down to three wells in a microtiter plate.

VaxDesign Inc and IAVI have entered into a partnership to test the system's utility for HIV vaccine research. As part of the collaboration, VaxDesign will first validate the system with known vaccines. If successful, the company will use it to help identify those HIV antigens that have the best shot at eliciting a broadly neutralizing antibody response in an eventual vaccine.

"At the heart of the [MIMIC system] modules are primary human immune cells," Mike Rivard, VaxDesign's vice president of corporate development, told BioWorld Today.

Each MIMIC system is derived from one blood donor. "Each module reflects the immune system of the donor," Rivard elaborated, "and we consider that a core strength," which allows the company to test antigens on models that mirror characteristics such as sex, race and age of the populations they would be used in.

Cells extracted from donated blood go into the first module, which models the vaccination site by reproducing key features of the innate immune system; it currently is built to mimic skin, though Rivard said that the company also plans to develop modules that mimic the lung and the mucosal system.

Once they are put into the first well, "monocytes spontaneously migrate through the endothelium and differentiate into macrophages and dendritic cells," Rivard explained. The dendritic cells in turn "spontaneously migrate back up into the supernatant." And when they do, they are ready to go into the second well, which mimics lymph tissue. In that second well, which consists of immune cells from the donor, "what you see is a process in which T cells and B cells interact with each other in a way that's very similar to what you see in a human lymph node."

The third part of the system is where the rubber meets the road. It consists of assays that "measure the effectiveness of the vaccine - whether you are getting the right kind of immune responses," Rivard said.

The company has tested its technology in a number of ways, including by investigating how well it recapitulates the immune system response to a number of influenza vaccines, and comparing it to peripheral blood mononuclear cell assays.

VaxDesign currently is testing how well the system's response correlates with individual serum titers from the same donor before and after vaccination.

In the programs' initial phase of one year, VaxDesign's first task will be to test the MIMIC system's response to rabies and yellow fever vaccines.

The goal is for the system "to recapitulate . . . the process of seeing those vaccines and making neutralizing antibodies," Koff said. If VaxDesign is successful, the partners together "will lay out a research program on HIV immunogens."

Koff noted that if the system works for HIV, it is also likely to work for a range of other antigens, which could expand its use further.

For now, Rivard said, VaxDesign's technology "would be used more at the discovery stage," to determine how different antigens interact with adjuvants, or with each other in multivalent vaccines. Longer-term, the system also could be used to understand why some people respond to vaccines while others do not. And while for the time being MIMIC system data cannot be used in the regulatory process, one of the company's goals is for its system to ultimately become an FDA-approved part of the preclinical discovery process.

"We're not there yet," Rivard said. "But we'll know we've really made it when the FDA accepts this as an animal replacement."