HIV-1 Vaccine– Good news!

No Debbie Downer HIV-1 post today!

The gods of HIV-1 research have a new paper in PLOS Pathogens, and to me, its real good news for those of us looking for an HIV vaccine.

Inflammatory Genital Infections Mitigate a Severe Genetic Bottleneck in Heterosexual Transmission of Subtype A and C HIV-1

Im probably going to do several posts on this paper (lots of cool findings), but I want to get this one bit of good news out there before some ass ‘science journalist’ mangles it :P

Haaland et al followed about 2,000 (2,000) discordant couples (one partner was infected with HIV-1, the other was not). At set points in time, they tested the non-infected individual for the prescience of HIV-1 and antibodies to HIV-1, hoping to catch transmission right when it happened so they could characterize what goes on, so we can figure out how to stop it.

Well, they found what they saw before– Of the 20 couples, 18 of the newly infected partners were infected with ‘one’ kind of virus (it could have been 50 viruses if they were all genetically identical– one genotype of virus). Of the other patients, one was infected with two genetically similar, but not identical viruses, and the other was infected with four.

The Good News
HIV-1 transmission is, in some ways, just a numbers game. Lots of viruses, lots of exposure, youre going to get infected eventually. But is the actual transmission event a numbers game? What I mean is, if Virus Variant A is the dominant genotype in a patients quasispecies, is Virus Variant A what gets transmitted?

If so, this is very bad news for those of us looking for a vaccine, because the dominant component of a quasispecies is different in every patient, every day. There is no way we could vaccinate for HIV-1, if this were the case. It would be physically impossible with todays knowledge and technology.

Good news! Because Haaland et al were following discordant couples, they had samples from the donors, as well as the recipients. So they went back to the donor samples and hunted for ‘the’ virus that infected the other partner… What got transmitted only made up ~5% of the donor quasispecies (if they counted donor sequences that were ‘close’, not just identical).

This means that HIV-1 transmission might not just be a probability exercise! There might be genetic determinants of transmission that we can identify and vaccinate against!

w00t!

Comments

  1. #1 dreikin
    February 2, 2009

    Hmm – makes me think of an interesting experiment:
    Take two diff (genetically) cell cultures that simulate skin -> blood -> T-cell path, infect one, let it develop, and then put it in intermittent contact with the clean one.

    Hard part’s prolly making the cells do that type of model..

  2. #2 Bob O'H
    February 2, 2009

    What got transmitted only made up ~5% of the donor quasispecies

    But if there were 20 quasispecies…

    I’ll await more. :-)

  3. #3 Poodle Stomper
    February 2, 2009

    Perhaps the highly transmitted groups contained mutations that made them more prone to being compartmentalized in the reproductive organs for some reason? I’ll have to read the paper. It sounds interesting.

  4. #4 example
    February 3, 2009

    Where the hell do they find these people?

  5. #5 rrt
    February 3, 2009

    This might be useful beyond HIV, no? Perhaps some other viruses will show the same transmission method?

  6. #6 Poodle Stomper
    February 3, 2009

    I read the paper last night and it does not appear that the transmitted strains are compartmentalized more so than any other strain. Interesting. Oh, and that smell we all smell? That is the smell of denialists crapping themselves trying to find an explanation for this paper that would fit their own distorted view.

  7. #7 Max
    February 4, 2009

    Maybe I’m reading it wrong, but it doesn’t look like their data indicate anything more than a numbers game… Like Bob O’H said, if what got transmitted represented only 5% of the donor quasispecies, but there were 20 quasispecies then you don’t have anything pointing towards a particularly infrequent variant being more frequently transmitted. If you look at table 2 there were actually anywhere from 35 to 45 quasispecies in the donors with matched infected partners whose infection was very similar to a donor variant. In fact, I don’t really see anything in there about the quantification of the individual variants in the donors, only how many variants there are, so it’s possible that a quasispecies that represents only 5% of the diversity could really represent 50% of the actual viral load of the donor.

    The authors say: “Because in a majority of cases a single donor variant establishes infection, we sought to determine the frequency of this variant or closely related variants in the donor quasispecies and to examine whether such variants predominated in plasma or PBMC derived viruses in the donor.” Reading this at first I thought the same thing you did, that they actually intended to quantify the presence of each quasispecies. But what they appear to mean is that they were just checking to see if the infecting quasispecies was specific to plasma or PBMC, which would imply a genetic determinant. They ended up with 6 of one and 4 of the other, which actually implies no determinant specific to the compartment the virus was isolated from. They didn’t check for any other determinants, so it’s not really bad news, but I wouldn’t say it’s particularly good news in the way you were suggesting :(

  8. #8 Drew
    February 4, 2009

    Very off topic but I found what might be the greatest atheist T-shirt ever; this might be the right crowd.
    http://www.tshirthell.com/funny-shirts/atheist/

    If you don’t want to click a link then just search for “Tshirthell” and “atheist”

  9. #9 adam
    November 20, 2009

    mum it’s great idea try to do more frankly it’s good news for
    us to minimize our headache