"We are trying to put together models of who tells who what to do and in what sequence. IDO is somewhere in this chain of events," says Dr. Mellor, the principal investigator on a five-year, $3.1 million grant from the National Institute of Allergy and Infectious Diseases to help dissect IDO's role. "I guess the simplest hope we have is that by manipulating IDO, in this case by blocking it, we can get T cell vaccines to work much better."
A study published in the Proceedings of the National Academy of Sciences in March supports the theory. An international team of researchers, led by the University of Melbourne, Australia, showed that a vaccine adjuvant given to help boost the efficiency of the influenza vaccine instead boosted IDO expression, hurting the vaccine's ability to provide flu protection.
"This suggests that vaccinologists may have been underestimating the potential efficacy of vaccines because vaccines themselves or adjuvants delivered with vaccines induced IDO that attenuated the host immune response and blunted development of protective immunity," Dr. Mellor says.
An IDO inhibitor, already in clinical trials for tumors, may be the adjuvant that really gives vaccine a kick, the researchers say.
They believe a sticking point for vaccines generally is that most are designed to activate T cells. While it seems like a logical approach, the fact is most T-cell vaccines don't work that well. Among their many roles, T cells are killer cells that recognize and hopefully eliminate infected cells, which can become infection factories. In fact, scientists believe T cell vaccines should prompt recognition and elimination of different s
|Contact: Toni Baker|
Medical College of Georgia