A team of researchers led by Dr. Todd Allen of the Ragon Institute of Mass General, MIT, and Harvard was recently awarded a 5-year, $12.4 million HIV Vaccine Research and Design (HIVRAD) award from the National Institutes of Health (NIH). The Ragon Institute is one of the institutions making Boston– with total grants of $1.78 billion received in 2012– the top NIH funded city in the country.
The proposal, entitled “Optimizing Human B and T Cell Vaccines Against HIV Using Humanized BLT Mice”, is designed to advance the field of HIV vaccine discovery research by studying the efficacy of various vaccine approaches to block and control HIV infection in the recently developed humanized mouse model.
As recently demonstrated, this novel small animal model simulates a human immune response to HIV, thus providing the unique opportunity to rapidly conduct iterative studies toward the development of an effective HIV vaccine. It also allows researchers to explore novel approaches to induce more effective immune responses against this highly persistent virus.
Since the mid-1980’s, the non-human primate rhesus macaque model has been used for HIV vaccine research. However, there exist substantial sequence differences between HIV and the SIV (simian immunodeficiency virus) that is used to infect these animals. This, combined with the sequence differences between human and macaque host genes, results in humans and macaques mounting immune responses against very different regions of HIV and SIV respectively. These differences impede efforts to translate promising research findings in macaques to identify critical areas of weakness in the HIV virus for human vaccine development.
Although the humanized mouse model was first developed in the late 1980’s, recent advances to the model including the ability to transplant functioning human genes, cells, or tissues into the mice, has enabled these mice to develop more robust human immune systems, including human-like immune responses to HIV infection. The result is a mouse model which can mimic the fundamental aspects of HIV infection in humans, as well as the early human immune response against HIV, and allow researchers to more effectively study the mechanisms of immune control and disease progression.
“The ability of HIV to rapidly mutate and shield susceptible regions from human immune responses continues to thwart efforts to develop an effective HIV vaccine,” said Dr. Todd Allen. “The ability of humanized mouse models to mimic human immunity to HIV provides the unique opportunity to study immune responses to HIV in a highly adaptable and cost-effective small animal model. This grant will allow us to further accelerate the study of vaccine immunity to HIV.”
The team of Ragon researchers headed by Dr. Allen also includes Dr. Andrew Tager (Massachusetts General Hospital), Dr. Marcus Altfeld (Ragon Institute), Dr. Dennis Burton (Scripps Institute and the Ragon Institute), Dr. William Schief (Scripps Institute), Dr. Darrell Irvine (MIT and the Ragon Institute), and Dr. Musie Ghebremichael (Ragon Institute).
It is hoped that this new grant to support the small animal model will accelerate research toward developing an effective vaccine for HIV/AIDS.
Of Mice and Men, VAX magazine
Of Mice and Man, Science News News
Science Update Podcast featuring Todd Allen
Will Humanized Mice Move Us Closer to an AIDS Vaccine?, IAVI Report
HIV-1-Infected Humanized Mice Mirror Human HIV-1 Infection, The Jackson Laboratory
Video: Humanized Mice Symposium, November 5, 2012