Animal model replicates human immune response against HIV, could revolutionize HIV vaccine research

July 18, 2012

One of the challenges to HIV vaccine development has been the lack of an animal model that accurately reflects the human immune response to the virus and how the virus evolves to evade that response. In the July 18 issue of Science Translational Medicine, researchers from the Ragon Institute of Massachusetts General Hospital (MGH), MIT and Harvard report that a model created by transplanting elements of the human immune system into an immunodeficient mouse addresses these key issues and has the potential to reduce significantly the time and costs required to test candidate vaccines.

"Our study showed not only that these humanized mice mount human immune responses against HIV but also that the ability of HIV to evade these responses by mutating targeted by CD8 'killer' is accurately reflected in these mice," says Todd Allen, PhD, senior author of the report. "For the first time we have an that accurately reproduces critical host-pathogen interactions, a model that will help facilitate the development an effective vaccine for HIV." Recent studies by Allen's team and others have revealed that of HIV is significantly limited by the ability of the virus to evade immune responses by rapidly mutating.

The traditional animal model for is the , which can be infected with the related simian immunodeficiency virus (SIV). But differences in viral sequences between SIV and HIV, along with differences between the human and monkey immune systems, limit the ability of the model to replicate directly key interactions between HIV and the . Development of an effective HIV vaccine will require a greater understanding of how human immune responses succeed or fail to control HIV.

The current study was designed to test the humanized BLT mouse, a model created by transplanting human bone marrow , along with other , into mice lacking a functioning immune system. Andrew Tager, MD, a co-author of the report and director of the MGH Humanized Mouse Program, explains, "Multiple researchers have contributed to dramatic improvements in the ability of humanized mice to model human diseases. Earlier studies with BLT mice performed at the University of Texas Southwestern Medical Center, the MGH and elsewhere have demonstrated that this particular humanized mouse model reproduces many aspects of the human ."

Timothy Dudek, PhD, of the Ragon Institute, lead author of the current study, adds, "Unlike normal mice, these humanized mice can be infected with HIV. But there has been little evidence regarding whether they reproduce the interaction between HIV and the human immune system, particularly the development of specific immune responses that exert control over HIV by targeting critical regions of the virus."

Tager's team at the MGH Center for Immunology and Inflammatory Diseases created groups of humanized BLT mice using cells and tissues from human donors with different alleles, or versions, of the immune system's HLA molecules, which flag infected cells for destruction by CD8 T cells. Particular HLA alleles, such as HLA-B57, are more common in individuals naturally able to control HIV, and some of the mice generated by Tager's group expressed this important protective allele.

Six weeks after the mice had been infected with HIV, the researchers found that the virus was rapidly evolving in regions known to be targeted by CD8 T cells. Their observation indicated that not only were the humanized mouse immune systems responding to HIV but also that the virus was mutating to avoid those responses in a manner similar to what is seen in humans. In mice expressing the protective HLA-B57 allele, just as in human patients who control viral levels, CD8 responses were directed against an essential region of the virus, preventing viral mutation and allowing the animals to more effectively contain HIV.

"We now know that these appear to replicate the specificity of the human cellular response to HIV and that the virus is attempting to evade these responses just as it does in humans," says Allen, an associate professor of Medicine at Harvard Medical School. "We are currently studying whether we can induce human HIV-specific immune responses in these animals by vaccination, which would provide a rapid, cost-effective model to test the ability of different vaccine approaches to control or even block HIV infection. If we can do this, we'll have a very powerful new tool to accelerate HIV vaccine development, one that also may be useful against other pathogens."

Explore further: Breast milk kills HIV and blocks its oral transmission in humanized mouse

Related Stories

Breast milk kills HIV and blocks its oral transmission in humanized mouse

June 14, 2012
More than 15 percent of new HIV infections occur in children. Without treatment, only 65 percent of HIV-infected children will live until their first birthday, and fewer than half will make it to the age of two. Although ...

Preventing the spread of HIV/AIDS with humanized BLT mice

May 18, 2011
The more than 2.7 million new HIV infections recorded per year leave little doubt that the HIV/AIDS epidemic continues to spread globally. That's why there's the need for safe, inexpensive and effective drugs to successfully ...

Engineered stem cells seek out, kill HIV in living organisms

April 12, 2012
(Medical Xpress) -- Expanding on previous research providing proof-of-principal that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers have now demonstrated that these cells ...

Hide-and-seek: Altered HIV can't evade immune system

September 28, 2011
(Medical Xpress) -- Researchers at Johns Hopkins have modified HIV in a way that makes it no longer able to suppress the immune system. Their work, they say in a report published online September 19 in the journal Blood, ...

Recommended for you

Scientists find where HIV 'hides' to evade detection by the immune system

October 19, 2017
In a decades-long game of hide and seek, scientists from Sydney's Westmead Institute for Medical Research have confirmed for the very first time the specific immune memory T-cells where infectious HIV 'hides' in the human ...

National roll-out of PrEP HIV prevention drug would be cost-effective

October 18, 2017
Providing pre-exposure prophylaxis (PrEP) medication to men who have sex with men who are at high risk of HIV infection (equivalent to less than 5% of men who have sex with men at any point in time) in England would be cost-effective, ...

Regulatory T cells harbor HIV/SIV virus during antiviral drug treatment

October 17, 2017
Scientists at Yerkes National Primate Research Center, Emory University have identified an additional part of the HIV reservoir, immune cells that survive and harbor the virus despite long-term treatment with antiviral drugs.

New research opens the door to 'functional cure' for HIV

October 17, 2017
In findings that open the door to a completely different approach to curing HIV infections, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time shown that a novel compound effectively ...

Researchers create molecule that could 'kick and kill' HIV

October 5, 2017
Current anti-AIDS drugs are highly effective at making HIV undetectable and allowing people with the virus to live longer, healthier lives. The treatments, a class of medications called antiretroviral therapy, also greatly ...

A sixth of new HIV patients in Europe 50 or older: study

September 27, 2017
People aged 50 and older comprise a growing percentage of HIV patients in Europe, accounting for one in six new cases in 2015, researchers said Wednesday.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.