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Gene Therapy Approach 'Completely' Protects Mice From HIV Infection

Pierre Bezukhov writes "Scientists from the California Institute of Technology have come up with a gene therapy approach that has proven effective in protecting mice (with humanized immune systems) against HIV infections. They used a genetically altered virus to infect muscles cells and deliver DNA codes of potent antibodies isolated from the blood of human HIV victims (abstract). The muscle cells then began to manufacture the antibodies in quantities that proved 'completely protective' against HIV infection. By contrast, traditional vaccines have not worked against HIV, as scientists have failed to find a molecule that induces the immune system to produce enough potent antibodies. The difficulties stem from the fact that HIV disguises some of its external structures from the antibodies."

20 of 190 comments (clear)

  1. How to conduct human trials by scorp1us · · Score: 4, Interesting

    How do you conduct a proper trial for HIV? "Here, this is either a drug that will work, won't work, or a placebo which works a surprising amount of time. At best you have a 50/50 shot of getting HIV" Who is going to participate in that trial?

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    1. Re:How to conduct human trials by scamper_22 · · Score: 3, Interesting

      You'll never get a proper scientific trial. There are whole areas of medicine we only know because evil regimes like the Nazi Germany conducted experiments without care.

      But you can certainly make a best effort. Inject 1000 random people with either drug, placebo...

      They do whatever they do. They can engage in risky behavior. They can wear condoms. Whatever is. As an experiment, you just assume their behavior is randomly distributed among the 1000 people.

      At the end of the trial, you call them back and see what percentage has AIDS/HIV.
      If all those who received the drug don't have it, and SOME of the ones without it did have HIV/AIDS, then you can say there is a high probability the drug works.

      As I said, statistically you just have to assume that behaviors were distributed evenly among the 1000 person sample.

      If no one comes back with HIV/AIDS... by some miracle that 1000 person trial... everyone suddenly behaves nicely and stops having unprotected sex, no one gets raped... well then the experiment is a failure, but at least 1000 people are not living a good life... so it's a human success.

    2. Re:How to conduct human trials by Jason+Levine · · Score: 4, Informative

      There have already been trials. You give the treatment to one group of at-risk individuals and a placebo to another group. You make sure that they understand that they aren't to rely on this as a cure/certain protection. Then you follow them over the years and see what the infection rate is. If 30% of the control group is infected with HIV at the end and only 5% of the treatment group is infected, you've got a good result. If they are both about the same, your treatment doesn't work.

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    3. Re:How to conduct human trials by robotkid · · Score: 3, Informative

      Nah, we just have to find blind corners of human civilization that nobody cares about. http://en.wikipedia.org/wiki/Guatemala_syphilis_experiment , http://en.wikipedia.org/wiki/Tuskegee_syphilis_experiment

      To do this in todays times... Guantanamo anyone?

      Not too off the mark. Prior trials on HIV prevention have been done on high risk populations in Thailand and Botswana. And these are studies sponsored by the CDC, not a rogue evil scientist as with the Guatemala experiments (whom, it should be noted, had absolutely no oversight even though he was using US tax dollars as these checks weren't required back then).

      http://www.cdc.gov/hiv/prep/resources/factsheets/pdf/prep.pdf

      Overseas trials do bring up a whole host of ethical concerns (especially when dealing with populations that have little or no access to healthcare - making participation in a trial perhaps the only way to see a real doctor). This is a real issue because usually the control population gets "standard of care" which is very different in the US vs the developing world. What's even shadier is that there have been allegations of drug companies secretly hiring shady doctors in the third world to enroll patients in highly risky studies that would never be approved in the US, and the patients often don't even know they were in an experimental study, they thought they were getting a proven treatment.

      At least, with the CDC trials, one can be assured that the participants are actually volunteers who gave explicit consent and had the risks explained to them (unlike those Guatemalan prisoners who had no choice), that the trial protocol passed review by external ethics boards both in the US and by the local governmental authority (again, unlike Guatemala where outside of a few prison officials the local gov't had no idea what was going on). Not that these are fool-proof checks in countries with unstable or nonexistent public health infrastructures and highly corrupt officials, but at least it's something.

  2. Re:Billions by mathmathrevolution · · Score: 4, Insightful

    Are you from 1982?

    Most people who get AIDS today are young heterosexual females. They are not "fucking random strangers in the ass without protection."

    AIDS is a disease that any sexually active person can get, even if they use protection. I don't sleep around a lot, but I have sex and unprotected oral sex. Why do you think my partners and I deserve to die? Because we are violating your personal moral code? Or because you are driven by resentment of your more sexually successful peers?

  3. Re:Can't Wait For The Peer Review by HBI · · Score: 4, Insightful

    The thought that occurred to me was: if your muscle cells have had a coding sequence for an antibody injected into them, aren't they now engaging in effort that has nothing to do with their primary function? Wouldn't that impact things in old age? Wouldn't that increase the likelihood of heart problems, perhaps?

    Then, one might think: why would you want to produce a boatload of HIV antibodies after your years of promiscuous sexual activity are over? Very few of us continue with that behavior ad infinitum.

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  4. Turning off Gene Therapy? by mathmathrevolution · · Score: 4, Interesting

    The article expresses a concern that once the gene therapy is started it can't be turned off if the person has an allergic reaction to the antibodies. Maybe somebody more informed can explain why:

    1) You couldn't test for an allergic reaction in advance of the gene therapy.

    2) You couldn't just do more gene therapy to turn off your original gene therapy.

    1. Re:Turning off Gene Therapy? by Anonymous Coward · · Score: 5, Insightful

      1: Allergic reactions tend to develop over time. You may not be allergic at first, but as a result of constant exposure, you may become so over time. Antibodies are small and soluble enough that this isn't usually a problem, but with a non-self fC region, they can be. We've seen this occasionally with the purification tags used in many common biotherapeutics; if your immune system begins to recognize the tag (his-6 is common) from one therapeutic, any other biologic with the same tag will cause an allergic reaction. Note: this doesn't normally occur with antibody-based therapeutics since they can be efficiently purified without being tagged.
       
      2: The thing about turning it off is that the off switch has to be hit in the same cells that are producing it; i.e. millions of separate sites. More gene therapy is unlikely to hit *all* of the same cells, and will potentially cause some unintended consequences in non-target cells. The solution is to use a molecular switch. If I were designing it, I'd flank the antibody promoter region and the transcription start site with loxP recognition sequences. Add a cre recombinase gene under the direction of an antibiotic-activated promoter. Basically this would allow you to reverse at least a portion of the gene therapy at will. Take an antibiotic and the affected cells would actually cut out the antibody producing region they introduced. Unfortunately, if you wanted to again have protection, you'd have to undergo the gene therapy again. You could do a similar setup using siRNA under a controlled promoter, but this scheme also has its drawbacks (repression of the transgene therapeutic would only be temporary - which could be better or worse depending on your goals). Anyway, whichever scheme you use will have to be introduced in conjunction with the original treatment; adding it afterwards won't work nearly as well due to the difficulty in getting the treatment to all of the affected cells.

  5. Promising, but... by FlavaFlavivirus · · Score: 4, Interesting

    This experiment will probably not produce an actual human drug, as it suffers from the same drawback as most previous gene-therapy studies: the Adenovirus transduction system will kill a significant number of patients. However, the results do seem to indicate that a monoclonal antibody has protective effects. The gene therapy vaccine may not work, but you could inject purified antibody into someone who had a known exposure, or is going to be in a high-risk situation, and prevent infection. Unfortunately, these types of therapies will never be able to cure an established infection, as HIV integrates its genome into host T-cells.

  6. Re:Billions by gyaku_zuki · · Score: 4, Insightful

    Jeez - and here I thought Slashdot to be a haven from this sort of nonsense. Seriously, you and your fellow 'Anonymous Coward's should have your human license revoked.

  7. Re:Gay Mice by gyaku_zuki · · Score: 5, Interesting

    I love how you decided to keep this comment anonymous. 'It's as if' you are scared to actually back up your opinion. Seriously, in the 'playground' version of being a fag, you are the biggest one I've seen.

    Gravity - 'It's as if nature doesn't think' humans should fly, but we do (planes).

    Fun fact - nature isn't CONSCIOUS. It doesn't really give a crap what you think or do. Nature didn't wake up one day and think 'hey, I think I hate queers today!'. Unless you're religious, then of course why I even waste my breath is beyond me.

  8. Re:Gene therapy is a preventive measure by betterunixthanunix · · Score: 3, Informative

    Unfortunately, the best ways to prevent HIV infection are not within the realm of what can reasonably be expected. People tend to have sex, to not be monogamous, and prefer not to discuss previous sexual partners. Condoms are highly effective but not perfect, and condoms substantially reduce the pleasure men feel while having sex (and I even know some women who do not like the feeling of a condom).

    The reality is that a vaccine or cure for HIV is needed in order for the disease to be eradicated. There is no other way to solve this problem. You will never be able to convince millions (let alone billions) people to be monogamous and to wait until marriage.

    --
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  9. "Scientists from Caltech"? by Christianson · · Score: 4, Interesting

    Maybe this is a silly, minor thing, but it bothers me these sort of blurbs always just talk about faceless "scientists." Does it really take that much work to find out who the principal researchers were? Maybe more people would be inspired to get into science if it actually seemed to come with some measure of face rather than anonymity in a lab coat.

  10. Re:Can't Wait For The Peer Review by cpricejones · · Score: 3, Interesting

    So the goal of the adenovirus is to introduce the broadly neutralizing antibody into T cell lines. These are the immune cells that are going to be ultimately fighting HIV infection, but they lack the right antibodies. In the normal situation, your body raises antibodies, but they cannot bind to the right spot on the virus envelope. Instead, they bind to a spot that the virus naturally varies, and the virus escapes via mutation (i.e., mutated virus replicates, other virus doesn't). In the new situation, the adenovirus provides an antibody that is better, which binds a spot on Env that the virus needs (so virus with mutation at this spot replicate poorly).

    So muscle and heart cells are likely not getting the vector, nor would they be expressing antibodies. Similarly, your body wont continue to raise the antibody if the infection is gone (it will not be ad infinitum).

    This is my understanding ... perhaps others could add key points.

  11. Re:Trouble is by nedlohs · · Score: 4, Informative

    It can't be cited other than by checking every single scientific study in all of history and seeing that nonw of them proof that ADIS is caused by HIV.

    it can be trivially disproved by showing the proof of course.

    For that we basically have Koch's Postulates.

    1. The germ must be found in every host with the disease
    There have been cases of of AIDS like symptoms without HIV:
    http://www.ncbi.nlm.nih.gov/pubmed/8093633

    They are very rare though, and just because something that isn't influenza can cause flu like symptoms doesn't mean influenza doesn't cause the flu.

    Essentially everyone with AIDS tests positive for HIV, and >99% of people without AIDS test negative for HIV.

    2. The germ must be isolated from the host and grown in pure culture
    This is done routinely .

    3. The germ must cause the disease when introduced into a susceptible healthy host.
    4. The germ must be re-isolated from the infected host

    Ethics prevent us from doing these steps for things we think will kill you.

    However, there have been a few lab accidents in which workers have been infected with HIV (cultured HIV, not just say blood from an AIDS patient getting into their bloodstream, which would carry more than just HIV). All of them showed T-cell depletion. And HIV was then isolated from them and matched the one they had been infected with exactly.

    http://gateway.nlm.nih.gov/MeetingAbstracts/ma?f=102203749.html

    Plus the dozens of health care workers who have contracted AIDS from mistakes with HIV+ blood/etc - clearly not as good as isolated HIV infection for showing it is HIV, but more volume.

  12. Re:Oh internets. by cayenne8 · · Score: 3, Funny
    Hmm.....

    It would be sweet if AIDS were no longer a threat.

    They day they announce the cure.....I'm guessing if you can't get laid that day...you're never gonna get laid.

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  13. Re:Gay Mice by sunderland56 · · Score: 5, Funny

    This is *great* news for gay mice. Ever try to put on one of those tiny little condoms without tearing it with your claws?

  14. This is a huge relief by Brooklynoid · · Score: 3, Funny

    Now I can have unprotected sex with mice and not worry about getting AIDS

  15. Re:Billions by dkleinsc · · Score: 4, Informative

    ... in the United States.

    That's where you go wrong: compared to southern Africa, where about 1 out of every 5 adults currently infected, the 50,000 per year in the US is almost negligible. And in that population, about 60% of all adults with HIV are women and girls.

    source.

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  16. Re:Billions by mathmathrevolution · · Score: 4, Informative

    1) Most people getting infected with AIDS aren't in the United States. They are in Africa and other underdeveloped regions.

    2) AIDS prevalence is not the same as the infection rate. The total AIDS prevalence is high among gay men for historical reasons. But young heterosexual women are now the most at risk demographic.