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Oral vaccines – awesome, but no panacea

July 28, 2010

ERV has a great post about a new paper in PNAS that details the mechanism of immunity granted by muco-Rice, a great solution for cholera protection in the developing world:

So scientists have been working really hard to create vaccines to cholera and ETEC, and a group of folks have figured out a really cool strategy– genetically modify rice to express part of the cholera toxin. When someone eats the vaccine rice, their immune system gets a cheat-sheet for what the real toxin will look like. Their body starts secreting IgA, antibodies that recognize the toxin, in their mouth/tears/digestive tract/breast milk. If that person is exposed to real cholera, they already have antibodies around to neutralize the toxin, thus are able to prevent or limit the extent of that infection!

BONUS: If the person who gets the vaccine is a breast-feeding mom, these beneficial anti-cholera-toxin IgA antibodies are passed down to their babies via breast milk, thus also protect their babies from cholera!

BONUS BONUS: This plant-based vaccine strategy is also beneficial because it requires no sterile needles, no freezing/refrigeration, and the vaccine would have a ridiculous shelf-life of at least three years.

Sounds awesome! Let’s make all our vaccines into food products – no needles, long shelf-life, cheap! Right?

Wrong. Unfortunately, this method will probably have very limited use. Most of the things you eat generate immune tolerance, not protective immunity. In fact, when so-called oral tolerance breaks down, you get food allergies. There’s so much foreign crap (pardon the pun) in your digestive tract that the immune system has evolved to actively ignore and suppress the immune response to the things you eat. But wait – what about the oral polio vaccine? That works because it’s a live-attenuated (weakened) virus. The virus actually causes a local infection, which pisses off the immune system and circumvents oral tolerance.

But Cholera-toxin is a protein, not a virus, so at first glance, it seems like it should induce oral tolerance. After all, you don’t have immune responses every time you eat a steak (unless you’re unfortunate enough to have a steak allergy – would life even be worth living?). But cholera toxin is special – it can invade cells on its own. In fact, that’s why it causes so much damage in the first place. When you’re infected with Vibrio cholera, it secretes this toxin which is composed of a bunch of different subunits (parts). The B-subunit is able to latch on to cells and get pulled inside, then the A-subunit punches a hole in the vesicle containing it and runs amok. This rice vaccine only uses the B-subunit, so it can invade cells and piss off the immune system without actually causing much damage (it does cause a little bit of damage, which is what alerts the immune system in the first place). This is great news for treating cholera (and a few other bacterial toxin-induced diseases) as ERV mentioned, but unfortunately any dreams of ditching needles for good will have to be put on hold.

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