Green our vaccines!

Antivaxers want green vaccines? How about vaccines produced in plants? Solar powered, green leafy plants-- Cant get much more green than that!

The basic idea is that we modify plants to make viral/bacterial proteins, and then we eat the plants, and YAY! Vaccine! How could this possibly work? Doesnt everything just get digested? Well, there are a lot of viruses/bacteria that need your intestines to infect you-- Polio, enteric bacteria like salmonella and E. coli and cholera, rotavirus, norovirus, etc. Then you have viruses/bacteria that just want some kind of mucosal site (eyes, mouth, nose) like HIV-1, RSV, CMV, all flavors of herpes, measles, common cold, influenza, Staph, Pseudomonas, Strep, etc.

You have sentinel immune cells embedded in your mucosal tissue, constantly sampling your inner outer surfaces, looking for something that could be causing trouble.

For example, say a dendritic cell in your gut picks up a chunk of an oral polio vaccine you swallowed. It presents this chunk to CD4+ T-cells who are all like "WTF IS THIS SHIT! DO NOT WANT!", and then it marches up to a lymph node to bitch out other T-cells and B-cells. The B-cells also get real pissed off, and start maturing from IgM/BCR expressing B-cells into mature IgG, IgA, IgE producing B-cells, making antibodies that recognize that chunk of oral polio vaccine. IgA is the antibody you secrete in your saliva (how fast HIV-1 tests work), tears, mucus, intestines, etc. And thats why, if youve had an oral polio vaccine and then you are exposed to 'wild-type polio', you dont get infected, much less sick, much less paralyzed.

Here is an image from a Nature Review relating to how this works (I think you can see this-- someone tell me if you cant).

So, if we get plants to produce viral/bacterial proteins that cause diseases in us, and we can get immunity to these bugs just by eating a potato or corn or some dried up arabadopsis, that would be pretty damn awesome. Not just because of the immunity, but because vaccines made this way instead of via tissue/egg culture 1) are cheap, 2) have a long shelf-life, 3) are stable in ambient temperatures, 4) insure we are going to get IgA protectivity, 5) dont need any needles (needles in the 3rd world... ehh...)... probably more advantages I havent thought of.

This idea has been around a long time (20 years-ish?), but there has recently been a big push for these kinds of vaccines-- as they could be made relatively quickly in response to new outbreaks (ie Swine Flu), or even provide cheap ways to vaccinate against bastards like cholera and malaria. We are even opening plant vaccine factories in Delaware and Texas.

NOMNOMNOM! Green vaccines!

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Is this a trick to make me eat my veggies? D:

And it would prevent the problems with egg allergies.

Yeah, but doesn't it give the plants autism? I mean, our plants have been moping around without saying anything for YEARS! Maybe they were vaccinated plants!!

By AZSkeptic (not verified) on 06 May 2010 #permalink

There's a company called Protalix that is planning on plant tissue culture vaccines. It's a cool system, and working now to produce the Gaucher disease treatment protein. The grow these carrot cells in big bags.

I've never understood--it's my ignorance--how people get sick from E. coli when it lives in everyone's gut.

If I were a creationist or an anti-vaxer or some other kind of science denialist I would say that it's obviously impossible for E. coli to cause disease. I'm not those things, so I looked it up on wikipedia and now I have some of the answer. The bacteria cause problems when they get into parts of the body they are not supposed to be in, and some strains produce toxins that don't breakdown with heat or in the gut.

Anyone with expertise who can explain it better, I'd love to here from.

By Gabriel Hanna (not verified) on 06 May 2010 #permalink

The gut is usually a very anti-inflammatory place, and just eating isolated antigens usually causes tolerance, not an immune response. It's even been shown that inducing oral tolerance to self-antigens can aid in prevention of auto-immunity. So this strategy really doesn't make any sense to me - it seems like it would do the opposite of what you want. Oral polio gets around this because it's a live virus, so it causes active infections.

@Gabriel - There are a bunch of different strains of E.Coli that live happily and non-pathogenically in the gut. Usually, they (and the other bazillion bugs that live in you) are separated from the tissues in your gut by a layer of mucous and anti-microbial proteins that are secreted when the bugs get too close. Pathogenic E.Coli (and other gut pathogens) can evade those barrier functions and can get down to and invade the tissue. The toxins they produce can also punch holes in the cells that line the gut, and that's what causes the bulk of the problem (and alerts the immune system that something is wrong).

Gabriel, I think it's because there are lots of strains of e coli. The ones we all have don't make many of us sick. The particular one that caused a big problem up here in Walkerton Ontario a few years back was a strain that cows are just fine with, but when manure wasn't cared for appropriately it got into a town's reservoir. Led to dead people and sick people because it wasn't one that our guts could handle. I think that strain was designated H157 O7 (or something vaguely like that... I may have the H part and O part swapped around).

Gabriel- although erv is, understandably, obsessed with erv related gene-swapping, it is far from the only kind. One way normally non-pathogenic bacteria can cause problems is if they acquire pathogen genes. For example, E. coli O157 happens to have acquired a plasmid from a nasty neighbor- Shigella- which encodes a gene that allows the E. coli to make Shiga toxin.
Regular E. coli in your gut do not have that toxin, and as long as they don't grow amuck (as they could in the absence of immune response, or if something very bad happens, like your gut getting ripped into your blood stream), you are fine (some of the mechanisms that prevent growing amuck- like immune tolerance toward abundant antigens in locations like the gut and mucosal surfaces with active immune cells preventing spread- have already been discussed. There's lots of interesting research going on in this area). But E. coli O157 is highly virulent- as few as *10* bacteria (a common infectious dose is more like 10^6!) can grow and produce enough nasty Shiga toxin to cause disease. It seems like a lot of the enteropathogens are toxin-dependent. But it's also important to recognize that the immune system is complex, and somewhat specialized by location. So an organism that is no problem in one area may be a threat in another area. I study malaria, and one of the big differences between Nasty Deadly Malaria and ho-hum I've-got-a-nasty-icky-fever malaria is whether the parasites manage to sequester into the brain. Cerebral malaria seems to be more common in children. It seems that both anatomical factors (children may have somewhat different tissue structures) and more direct immune factors (children are less likely to have effective antibodies) may allow the nasty parasites to get into a particularly hazardous place in kids, which is one reason malaria is particularly dangerous for children.
Interestingly, after you get bit by a mosquito, malaria parasites head straight to the liver. They hang out their for days, and you get no real symptoms. The immune system just doesn't 'see' them in the liver (there's interesting work on tolerance and liver, and the hepatitis people would LOVE to understand this stuff better). Then the parasites get into the blood stream and start activating the immune system crazymad.
So the disease has very different symptoms depending on what part of the body the pathogen gets to.

So to summarize:
1) not all E. coli are created equal
2) the same E. coli in different parts of the body will have different effects (I didn't even get into what normally benign E. coli can do to your bladder. Mostly cause it reminds me of catheters... BAD TIMES. *shudder*)

Nice try Erv, but no dice. Those would be evil gene-modified plants, activating the Monsanto response, patented genes, black helicopters, dogs and cats, Sodom and Gomorrah, gay marriage, end of world, Jerry Springer ...
Needles are easier, trust me.

@Gabriel and others on E. coli

The Shigella and Escherichia "genera" of bacteria are not truly separated by history, like Homo sapiens sapiens is from Pan torglodytes and Gorilla gorilla.

Shigella and Escherichia are essentially the same genus except for whether or not they encode the "Shiga toxins" which are often carried on plasmids, not the main chromosome of the genome. It is not ONLY the 0157:H7 isolate of E. coli that can carry the shiga toxin plasmid. And it is not yet clear how often this bacterial strain moves around, in comparison to how often this plasmid jumps from one bacterial host to another.

But anyway, the names "E. coli" and "Shigella flexnerii" do not cover just one "species" of bacteria each. They cover a wide range of different bacteria, linked together more by pathology phenotype, than true genetic ancestry.

@6,7,8: thanks, that helps.

By Gabriel Hanna (not verified) on 06 May 2010 #permalink

Cue the unintended consequences in 3...2...1...

No, seriously. What about evolution? Previously we were just immunizing ourselves (well, and food animals). Now we're potentially introducing this antigen into the whole environment. What if a plant virus takes this antigen and moves it somewhere else? I'm not concerned about the disease going extinct, but perhaps forcing the rapid evolution of the wild-type disease "pool" that isn't found in humans. It doesn't apply to polio since it is only found in humans, but imagine if we made Duckweed a flu vaccine carrier. I can't imagine it taking very long before Nature finds a way around it!

By Richard Hendricks (not verified) on 06 May 2010 #permalink

@12: there aren't a lot of viruses that can transfect between plants and people. If anything this approach should be even safer than using animal tissue cultures.

The long shelf life and stability are probably the most important factors for third-world applications; not having to maintain a cold chain would make things so much easier.

By Stephen Wells (not verified) on 06 May 2010 #permalink

OT, but I thought from the headline you were going to say how producing vaccines is currently energy-consuming and polluting, and how it could be made not so. But anyway...

It's a nice idea. Very good for third-world countries or disaster relief - fruit and vegetables keep fairly well. You can keep an apple out of the fridge for three weeks before it goes nasty. You would probably want to keep the vaccine-fruit and veg away from wild populations though - unless there's a way we can drop vaccines into harvested fruits and veg.
Which is even nicer. I'm a syringe phobe, and I've been skipping out on vaccinations since I was 12. I know it's a bad thing to do, because one of these vaccines could potentially save my life, but I can't stand the actual injection. If I could eat a nice piece of apple or peach instead, I'd have caught up with all of my immunisations years ago.
And, as someone above said, it'd be great for people with egg allergies. It'd also be great for little kids (who I can say from experience do not like having things stuck in their arms) and for syringe-phobes like me.
Lastly - and this is assuming it gets taken up widely - it could turn out to be cheaper than current immunisations. More in the realms of delivery and storage (at the moment, some governments are trying to push everyone to get swine flu shots ASAP before the vaccine goes bad and has to be disposed off) than creation, but it's something.

BUT. As others have said, oral vaccines don't work for everything. So I'd say do it for what it will work for, and...ehhh, just stick to the damn needles for the rest.

Now we're potentially introducing this antigen into the whole environment. What if a plant virus takes this antigen and moves it somewhere else?

Why would an antigen for humans do anything for a plant? Might as well worry that the vaccines will cause humans to sprout leaves.

By Gabriel Hanna (not verified) on 06 May 2010 #permalink

Quiet Gabriel you're gonna ruin it.

By pod people (not verified) on 07 May 2010 #permalink

@Richard Hendricks & Gabriel:

Antigens are just proteins or pieces of proteins that the immune can recognize, they don't necessarily have any function. The idea for this (and all vaccines really), is to show your immune system what to look for, so that when it encounters an actual bug with that antigen, it will be pre-programed to see it. So making plants express a flu antigen would never turn plants into carriers for the flu virus. That said, if other animals that are carriers for the virus, there's a chance that resistance could grow in animal populations (viruses might mutate so they wouldn't express that antigen), but that would just make the vaccine less effective, not create a super-bug.

@ERV, I think you got this a bit wrong. The paper (and the two factories you linked to) are using plants to make the antigens, but then the antigens need to be purified and put into conventional (ie needle-based) vaccines. This still has plenty of benefits, but just eating the plants would probably not work for the reasons I mentioned earlier.

@Kevin: perhaps if one was to have the plant produce chimeric virus fragments, with the antigen of choice fused to whatever it is the polio virus uses to transfer from the gut wall to the bloodstream, or the flu virus uses to cross the oral/nasal mucosa...?

By Tristan Croll (not verified) on 07 May 2010 #permalink


The polio vaccine is a live (attenuated) virus. It's certainly possible to engineer viruses to express other proteins (heck - I did it this morning), but (I think) getting a plant to assemble intact viruses would require actually getting the virus to infect the plant. Then it would also need to be able to infect the person. As someone mentioned earlier, the viruses that infect people are very different from the ones that infect plants.

I'm afraid we may be stuck with needles for a while longer :-(