There is a certain, rare class of individuals infected with HIV whose immune systems seem to do a better job of keeping the AIDS virus in check. Members of this group of HIV-infected individuals, commonly referred to as "elite controllers," live longer with the virus with fewer early complications. Now, researchers have bred an experimental mouse with a human immune system, which they hope will lead to the development of an HIV prevention vaccine modeled on the immune systems of elite controllers.
The new "humanized" mouse model was created by transplanting portions of the human immune system into immune-deficient rodents, including stem cells from bone marrow, as well as liver and thymus tissue. The thymus is a large gland at the bottom of the throat that "trains" T-lymphocytes, or T cells, to attack unwelcome microbes.
By using these so-called BLT mice, researcher Todd Allen says scientists will be able to see exactly how the human immune system responds to the AIDS virus and how the pathogen evades destruction by natural defense mechanisms.
Allen, who works with the Ragon Institute of Massachusetts General Hospital, MIT and Harvard University, says researchers hope to learn, for example, why the immune systems of some HIV-infected individuals manage the virus better than others.
"Some people termed ‘elite controllers’ are able to control HIV very well, to very low [viral] copies," he said. "And what we know is that they express a kind of host genetics that dictates that they target very critical regions of the virus."
Until recently, HIV research was primarily conducted in rhesus macaques. The monkey seemed to be a good human stand-in because the macaque could be easily infected with a primate version of HIV called simian immune-deficiency virus, or SIV. But differences in the genetics of SIV and HIV, as well as the human and monkey immune systems, mean SIV-infected macaques are not the best model for studying HIV.
Allen says the newly created mouse model accurately reflects what happens in humans infected with the AIDS virus.
Thanks to primate research and studies of how the virus attacks human cells, Allen says scientists now know a great deal about how well an individual’s genetic make-up determines their immune response to HIV, which they hope to further investigate in the humanized mouse.
"So it allows us to take all the discoveries we’ve had in studying individuals infected with HIV in the different immune responses and host genetics that correlate with a better outcome, and translate that now into an animal model where we can actually further manipulate that to understand how these individuals are actually doing that," he said.
And hopefully translate that information into an HIV vaccine.
An article published by Todd Allen and colleagues on the creation of an experimental mouse with a human immune system is published in the journal Science Translational Medicine.