When Good Antibodies Go Bad: Antibody-Dependent Enhancement

Posted by ERV on February 19, 2010
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Antibodies are normally a good thing. Neutralize viruses and bacterial toxins, tag bacteria for complement so they get blown up, tag invading parasites/worms/ew so your immune cells can kill them, antibodies even make nice cancer therapies.

One of the great things about antibodies is that the cells that make them? They ‘remember‘ what theyve seen before. Thats how vaccines work– you expose someone to a crappy polio virus, your body figures out how to neutralize it, and if youre exposed to Real Virulent Polio, your body has a cheat-sheet. Your body already has memory B-cells that know how to neutralize the virus, it doesnt have to scramble to figure out a right answer while the Real Virulent Polio is causing disease. Thus, if you get your polio vaccine, you will never experience disease caused by the polio virus, even if youre exposed to it.

But things dont always go according to plan, like with Dengue viruses:

Enhanced Infection of Liver Sinusoidal Endothelial Cells in a Mouse Model of Antibody-Induced Severe Dengue Disease

Normally, the more you are exposed to a virus, the milder the disease gets, if you get a ‘disease’ at all.

The exact opposite happens with dengue.

There are four ‘flavors’ of dengue. The first time youre exposed, you have very mild symptoms, or you might be totally asymptomatic. The second time youre exposed to dengue, if its a different flavor, you start getting the severe symptoms– fever, aches/pains, rash, and potentially death.

That makes no sense, right? Youre supposed to get sick the first time youre exposed, and not sick the second/third/fourth time your exposed. Whats going on?

The four flavors of dengue are closely related, but they are still different. Your body keeps making antibodies to the ‘same’ parts (antigenic sin), when its the different parts that mediate infection. So after your second infection, your body is making antibodies that cant neutralize the viruses anymore.

Furthermore, the non-neutralizng antibodies sticking to the viruses give the viruses an advantage: before, they could only infect cells that had just the right attachment molecules on the host cell surface. Non-neutralizing antibodies attached to viruses cause them to ‘stick’ to cells they normally couldnt infect… and the cell the virus is stuck to is now susceptible to infection.

Antibody-Dependent Enhancement.

… So what does this mean for vaccine design??

Anything but a ‘perfect’ vaccine could cause more severe disease after exposure, instead of preventing infection! It might mean we need to avoid making vaccines that elicit an antibody response, and shoot for a CTL vaccine instead.

What Zellweger et al have done is create a small animal model we can use for studying that very question. Their mouse model exhibits the same symptoms/pathology of dengue fever in humans. Theyve not only provided a means for collecting data that would otherwise only be available via autopsy, but a model for studying potential dengue vaccines and potential therapies for patients suffering from dengue fever. Sweet!

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Comments

  1. #1 Optimus Primate
    February 19, 2010

    Fascinating.

    Semi-related question: is there any rough geographic separate between the four flavors of dengue? Or are you just as likely to get infected with one variety in any particular tropical locale as you are any other?

  2. #2 Jared
    February 19, 2010

    There’s also the chance of using anti-sense morpholinos
    http://jac.oxfordjournals.org/cgi/content/full/62/3/555

  3. #3 Joe
    February 19, 2010

    [insert badly splelled lnog angry rant about how even pharma-shill Abbie has to admit that vaccines are toxic and make the disease WROSE!]

  4. #4 Ian
    February 19, 2010

    Thanks so much Abbie. I’ve never quite made sense of the statement that you’re more likely to get DHF the second or third time you get dengue. I’ve had dengue, and although the doctor told me I was barely sick enough to have dengue, it was by far the sickest I’ve ever been. Had a friend who got both malaria and DHF when he was in Guatemala (iirc). He said the malaria was much more pleasant. Apparently bleeding through your pores isn’t fun.

    @Optimus Primate – no, they aren’t separate, and it’s always a real concern when two (or more) strains are active in the same area.

  5. #5 Optimus Primate
    February 19, 2010

    Thanks, Ian. Also thanks for reading through my ridiculous typo. :)

  6. #6 ERV
    February 19, 2010

    Dont thank me, Ian! Thank these researchers! This is one of those things that has been hypothesized for a long time, but until we got a small animal model to really study this phenomena, it was just a ‘this makes sense but we cant prove it’ idea!

    Jared– Sweet!

    Joe– Not only am I under the control of BIG PHARMA, vaccines are also part of the Evilutionist Conspiracy!

    Optimus– Ian got your Q first, so… heres a funny picture that has been making me laugh for a couple of days :D

  7. #7 Optimus Primate
    February 20, 2010

    There’s only one thing that could make that any cuter: Pug Head Tilt!

  8. #8 Kevin
    February 20, 2010

    It just goes to show that whatever evolution our immune system goes through, the bugs are always better at using it for their own nefarious purposes.

    @Joe – I suppose you’re one of those people that thinks a blizzard in D.C. means global warming is bunk eh? “One rare disease can use anti-bodies to make things worse, therefore 200 years of vaccine science is completely wrong.” Yeah, that makes sense.

  9. #9 Cain
    February 20, 2010

    @8 Kevin,
    I suppose Joe was being sarcastic.

    Clue 1: ERV is a well know shill for the multinational puppah treats industry. We all know multinational evil cabals demand monogamy.

    Clue 2: IT’S THE MOST OBVIOUS THING EVER WRITTEN!

    …could be wrong though

  10. #10 Jared
    February 21, 2010

    It’s weird when I remember research papers I have read which are related to other research… Kind of like when you’re playing catch with someone and you forget to catch the ball as it hurdles toward your face. Then you are suddenly faced with the realization that now you have to go find the ball.

    Tangentially related, I wonder if any other viruses behave in this way–ouch.. back with the ball when I am no longer typing from my phone.

  11. #11 kimmy d
    February 22, 2010

    All vaccines have the potential to be harmful and even deadly to some people. While it is a fact that vaccines have almost eradicated many diseases and have saved countless lives, it is important to remember that they are not a panacea and everyone should be aware of the risks they pose to good health and immunity for some. Hopefully, the voices of the manufacturers of vaccines will be superseded by wellness practitioners and the medical establishment will be able to find a happy medium in the vaccine debate. In the meantime, we all need to remain informed and understand that vaccines are NOT compulsory, regardless of what most doctors, school districts, and pharmaceutical companies say. We all have the right to refuse them for ourselves and our children.

  12. #12 kimmy d
    February 22, 2010

    This is a very exciting post, btw, thank you ERV. I’m intrigued by the way organisms develop and defend themselves against us! Maybe we are really the “bad guys?” Hahaha! Maybe I’ve read too much Sara Blaffer Hrdy?

  13. #13 The Health Dude
    March 8, 2010

    “Health is wealth” is known to all and everyone wants good health. That means no one wants to leave this wealth. So, Let us build a food habit discipline, keep pace with work, rest and or exercise to Achieve good health, The ultimate wealth.