VIDI staff scientist Dr. Greg Spies is working on building a better HIV vaccine, starting from the individual DNA and protein pieces that make up the vaccine molecules. Along with other scientists in VIDI co-director Dr. Julie McElrath’s group, Spies is trying to figure out whether there is any connection between the common virus adenovirus 5, which has been used as a backbone for many candidate HIV vaccines, and infection with HIV.
Since results from the Step study, a trial for a potential HIV vaccine that used an adenovirus 5 vector, was halted in 2007, have come forth, there’s been a lot of rearrangement in the HIV vaccine field, Spies said. In addition to not providing protection against HIV, the vaccine used in the Step study seems to have actually increased the chances of HIV infection for uncircumcised men who had previously been exposed to adenovirus. Understandably, these findings prompted concern in the vaccine research field, and scientists have been trying to find out whether there is a true connection between adenovirus infection and HIV acquisition in trial volunteers who received the adenovirus-based vaccine.
In one approach to this question, Spies has been looking at the levels of adenovirus 5 antibodies, a measure of adenovirus infection, present in the blood of trial participants and compared these levels to the participants’ chance of becoming infected with HIV. For both volunteers who had received the vaccine and those who had received the placebo, Spies found no correlation between presence of adenovirus antibodies and chances of HIV infection, lending additional credence to the view that there is no real connection between the two viruses.
Because of the possible safety issue and because adenovirus-based HIV vaccine have proved fruitless in the past, researchers are now exploring other avenues for vaccine vectors, the backbones to deliver the vaccine pieces, Spies said. “We’ve spent a huge amount of time studying adenovirus and not studying HIV,” he said. “It’s good that we’re finally moving forward.”
Vectors for potential HIV vaccines are often made out of pieces from other, more innocuous viruses such as adenovirus, with the idea that those virus pieces may kick the immune system into gear and cause it to better recognize the pieces of HIV virus in the vaccine. Now Spies and other scientists are looking for alternatives to adenovirus as that backbone. “It was a real rock as a vector,” he said. “Other vectors are not yet up to that standard.”
In his role as Scientific Director for McElrath’s project under the Collaboration for AIDS Vaccine Discovery, Spies is looking into using the yellow fever virus as an HIV vaccine vector. To start, he’s testing it out in monkeys, creating an animal vaccine using parts of the “gag” protein from SIV, or Simian immunodeficiency virus. “The yellow fever vaccine has always held up as one of the most effective vaccines,” Spies said.
This isn’t the first time people have tried tweaking the yellow fever vaccine to make other vaccines – it has been successfully used to make an experimental Dengue vaccine by replacing the Yellow Fever envelope with the Dengue envelope. The first step to test the yellow fever-based vaccine will be to compare its immunogenicity to adenovirus vaccines in mice.
In another project, Spies is working with Dr. Harlan Robins, assistant member in Public Health Sciences and computational biologist, on integrating human genetic sequences into HIV vaccines that will cause increased production of the HIV proteins inside the human body, to give the immune system more protein to grab hold of. Researchers in the past have already come up with ways to increase protein production in HIV vaccines, but these novel sequences should in theory boost protein expression even higher, Spies said.
Although Spies started out in a different field, having earned a PhD in microbiology from Washington State University studying insect diseases for pest control, he’s been working on vaccines for a long time. After his PhD, he worked at the University of Washington with Clinical Research member Dr. Martin Cheever on cancer vaccines, and then moved to Corixa, a biotech company that studied the body’s immune response to protein pieces overproduced in cancer cells. When GlaxoSmithKline bought Corixa in 2005, Spies moved to his current position studying HIV at the Center.
He is also the study director for an assay that tests for the presence of adenovirus 5 antibodies, to determine whether study participants have been infected with that virus or not. Since the Step study, all further HIV vaccine trials using adenovirus vaccines are only enrolling people that haven’t been infected with adenovirus, due to the possible safety concerns. So anyone who wants to volunteer for one of these studies has to be screened for adenovirus first.