Novel Genetics Research Advances Possibility Of HIV Vaccine

[J220]

Great, great news...they are getting closer!

From http://www.sciencedaily.com/releases/2007/07/070706081332.htm :

Novel Genetics Research Advances Possibility Of HIV Vaccine

Science Daily — A pioneering collaborative study has discovered how the HIV virus evades the human body's immune system.

The research collaborative -- involving scientists from the British Columbia Centre for Excellence in HIV/AIDS, Massachusetts General Hospital (MGH), Microsoft Research and Los Alamos National Laboratory -- used highly computer-intensive, cutting-edge statistical research methods to investigate how the HIV virus mutates to escape the body's immune system.

Specifically, "HLA class 1" is a controlling part of the human immune response. The ability of HIV to escape recognition by HLA class 1 leaves the body incapable of finding and fighting the virus.

The study, published in the July issue of PLoS Pathogens, is the largest population-based investigation of how natural variations in HLA class 1 can influence HIV genetic sequence, as well as the first characterization of changes in multiple HIV genes in response to HLA-associated evolutionary pressure.

Researchers successfully mapped sites within particular HIV genes where variations can improve the virus's ability to escape immune recognition, showing this is predictable based upon the HIV patient's individual HLA class 1 profile.

"This is a novel and advanced description of how the human immune system attacks the virus, and how it responds" says Dr. Richard Harrigan, Director of the Centre's Research Laboratories and study co-author. "While we always knew the body attacks the virus and the virus changes to dodge pressure, we're now more exact in knowing how this happens in people."

While the study is valuable in helping the scientific community understand how immune pressure impacts HIV, these findings hold tremendous promise in terms of global HIV efforts, says Dr. Zabrina Brumme, the study's lead author. "Achieving a more in-depth understanding of the ways in which HIV mutates to avoid the human immune system will help with the design of an HIV vaccine," says Brumme, who is now with the Partners AIDS Research Center at MGH.

Data were collected from the British Columbia HOMER cohort, a large group of chronically HIV-infected, treatment-naïve individuals for whom HLA class-1 typing and HIV RNA genotyping were performed.

Microsoft Research provided personnel and advanced software tools to perform highly sophisticated statistical analysis. Algorithms developed by David Heckerman, lead researcher of the Machine Learning and Applied Statistics Group at Microsoft Research and study co-author, and his team allowed for more in-depth analysis of the data sets. "We created the software tools to help researchers exploit the power of computing to more quickly and accurately identify the crucial elements of an effective HIV vaccine," said Heckerman.

The original idea for the development of these statistical methods came from Dr. Bette Korber at Los Alamos National Laboratory. Korber and co-researchers Dr. Tanmoy Bhattacharya and Marcus Daniels worked with Heckerman in further developing the cutting-edge statistical approach.

Study results demonstrate that population-based approaches could complement smaller functional studies by providing a whole-gene or whole-virus picture of immune escape. Previous B.C. Centre research published in The Journal of Infectious Diseases investigated the role of HLA class 1 variation on response to anti-HIV therapy. "Moving forward, we'll be expanding our genetic research to other HIV genes. We'll also be investigating the role of drug therapy," says Harrigan.

Note: This story has been adapted from a news release issued by Massachusetts General Hospital.

[J220]

I found the original article from the authors of the study. It's very heavy on science jargon, but interesting nonetheless. The basic premise of this study, is that the specific mutations which cause HLA Class 1 to miss the virus (and hence cannot destroy it) appear to follow a predictable, addressable path. This is a major step in the right direction, and we will probably see this in the major media outlets in the next few days.

http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.ppat.0030094

[J220]

Wow, no replies to this thread? Am I the only one excited about this? This is huge, IMO. They have found how the virus evades the immune system, this is the first step in developing a vaccine that works!!!! Oh well...

[redhotmuslbear]

Wow, no replies to this thread? Am I the only one excited about this? This is huge, IMO. They have found how the virus evades the immune system, this is the first step in developing a vaccine that works!!!!

Yes and no.  With other bugs that do not mutate rapidly as a normal defense, vaccines train the body to produce components that will bind with certain protein sequences of the virus.  However, if HIV is changing these sequences many times, even in a predicatble manner, a vaccine will need to carry all of those combinations in order for a human immune system to respond to and suppress them all.

[J220]

Very good point. The hope is, of course, that either a hitherto unknown commonly-preserved area of the mutations is discovered, in order to target this with a vaccine, or that a method is devised to make all these mapped mutations recognizable by HLA class 1, thereby allowing the immune system to attack the infection. From what I gather, the problem is not that the body is not able to kill off the infection, it's that the virus mutates and escapes detection. Now that they know how the virus mutates exactly, and now that this is in fact predictable based on the particular HLA class 1 profile, it is possible that this could lead to a way to find a common marker in all mutations, and use this to elicit the proper immunological response. I believe this canl lead to some great therapy candidates. Cheers, J.