Oh for Petes sake.

*sigh*

Okay, there are two potential targets for an HIV-1 vaccine:

1– The envelope protein. Its the only HIV-1 protein that your antibodies can see. Antibodies can prevent the viruses from attaching to your cells.

2– The structural proteins in gag. These proteins are presented really well in MHC I molecules of infected cells. Thus cytotoxic T-cells will roll along and kill any cell thats infected with HIV-1.

Your body will react to HIV-1 in this manner ‘naturally’, without a vaccine. The problem is, the ‘natural’ response to HIV infection is reactive– Its always a step behind the mutational capabilities of the virus.

The idea with vaccines is to make your immune response to HIV-1 preventative. Make sure a cytotoxic T-cell is there to kill the first infected cell. Make sure antibodies are circulating in your bloodstream to neutralize the first HIV-1 virus introduced into your body. Stop the infection before it starts.

Well, there have been over 80 clinical trials of HIV-1 vaccines since we first started trying. They have been spectacular failures.

Whats the deal?

Well, its not just about ‘having antibodies there’ or ‘having CTLs there’– its about having the right antibodies and CTLs. Your B-cells (make antibodies) and T-cells go through all kinds of genetic rearranging tricks, and will eventually figure out a good combination, but what if we game the system? What if we dont wait for your body to figure out how to make the ‘perfect’ cytotoxic T-cell? What if we give it the right (a right) answer?

We can do that through genetic engineering.

Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor.

IF you have a particular MHC I type, in the case of this study, HLA-A*02, we know CTLs respond really well to a specific epitope in gag, ‘SLYNTVATL’. They found T-cells in an infected individual who was controlling HIV-1 really well that responded to that epitope. So they cloned out the T-cell-receptor arrangement, and when they put this TCR gene in new T-cells, the new T-cells responded to HIV-1 infected cells really well.

Theoretically this means we could isolate T-cells from infected individuals, transform them into super-anti-HIV-T-cells (or pimped-up souped-up bionic assassin lethal weapon killer T-Cells, if you will), and that could be an alternative therapy for HIV-1 infected patients. These ASSASSIN CELLS OMFG would go on a killing spree in the infected patient, killing every HIV-1 infected cell they came into contact with.

CURE FOR HIV-1 YEAAAAAAAH!

Ugh, no.

It gives us hope, and a new avenue to explore.

But we dont know if this will kill all HIV-1 infected cells. We dont know how preventative it is. We dont know what the cancer risks are (new genes into cells can = cancer). And, this therapy, even if it worked reasonably well, is quite impossible in Africa, SE Asia, etc. Places that need the most help.

So pimped-up souped-up bionic assassin lethal weapon killer T-Cells for HIV-1 is a really cool idea, but again, appreciate it as a cool idea and cool science that is contributing to the elimination of HIV-1. Not as a CURE FOR AIDS OMFG!

Comments

  1. #1 Paul Lundgren
    November 14, 2008

    “Pimped-up souped-up bionic assassin lethal weapon killer T-Cells” doesn’t roll off the tongue quite as well as “Teenage Mutant Ninja Turtles,” does it?

    Kawabunga!

  2. #2 esd29a
    November 14, 2008

    Apologies if I missed it in my quick glance through archives – Have you done a post on what a “works in Africa” therapy would have to be like?
    Large variability and mutation rates of HIV + not nearly enough money for individualised treatments = need to have a catch-all HIV-suppressor ?
    Or perhaps a treatment that concentrates on the more damaging virus variants, expecting that they will evolve in a patient that lives long enough – but that requires knowing these damaging variants in advance?

  3. #3 The Backpacker
    November 14, 2008

    Man you are a downer here people are working hard to invent really complex heart stopingly expencive cures and all you can say is that it won’t work in places where spend less on food in a year then I spend on coffee in a week. ERV you are just too much of a glass is all empty kind of person. On the bright side if the economy does not turn around soon none of us are going to have any money.

  4. #4 William Wallace
    November 15, 2008

    The path I would pursue if I were an evolander biologist.

    Genetically modify the virus through micro evolution, such that the new virus will have a competitive edge over the wild virus, but is susceptible to some drug or cocktail, or the natural immune system

    If necessary, in the later case, temporally suppress the immune response to the mutant with drugs, to provide the environment that provides a reproductive edge for the modified virus.

    Inject the mutant version of HIV, which will become dominant.

    After no traces of the wild strain are detected, give the drug cocktail known to be baneful to the mutant HIV, or stop suppressing the bodies immune system, and let it do its job.

    Then pray that the patients don’t go spreading the mutant by continuing their unhealthy lifestyle.

    Oh yeah, why not explain some of the acronyms? It’s a practice of good technical writers—more so if you’re writing for a general audience.

  5. #5 martinj
    November 15, 2008

    Wallace:

    ERV — Endogenous Retrovirus
    HIV — Human Immunodeficiency Virus
    AIDS — Aquired Immunodeficiency Syndrome
    MHC — Major Histocompatibility Complex
    HLA — Human Leukocyte Antigen
    CTL — Cytotoxic T Lymphocyte
    TCR — T Cell Receptor
    CD8 — Cluster of Differentiation 8
    GAG — Group Specific Antigen
    OMFG — Oh My F–ing G-d