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:
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.
… 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!