Genetic engineering meets vaccinology: or how to get the attention of all kinds of protesters

ERV wrote yesterday about a cool, new genetically-modified food that has the potential to act as a vaccine against cholera. The basic idea is that they are expressing a gene from cholera in rice. When you eat the rice, you are exposed to the fragment of a protein from cholera and will make antibodies to it. That way when you are exposed to cholera in the future, you will be immune to it. What are the advantages of this approach? From ERV:

So really this rice is going to be ground up and put into pill form, which is fantastic on so many levels!

1. Dont need a needle. Ive said over and over and OVER (are you listening, HIV-Circumcision 'researchers'??) its really damn hard to make sure your needles/equipment is appropriately sterilized in the third world. I dont care how many seminars youve had on how to sterilize needles. It doesnt always get done. Plus, I dont think youll hear any kids complaining about a lack of needles ;)

2. Can be kept at room temperature. No refrigeration. Aint gonna always have that in the third world either. Sure you might have a fridge, but it might not have power. And they tested batches that were left at room temp for 1.5 years-- Still worked. AWESOME!

3. Introducing the antigen through the intestinal mucosa. These folks found that introducing the cholera antigen orally works great because cholera normally infects through your digestive tract! Convinces lots of sentinel immune cells to hang out in your intestine and wait for another cholera bug to float by!

I thought I would write about another super cool approach to vaccines of the 21st century, and this one is a little closer to home as my wife and I both work on things that are indirectly related to this. (Though I confess, I'm a little worried that this post will attract the anti-vaccination mob along with the anti-genetic-engineering crowd).

Live-vector vaccines are what a lot of folks are hoping will be the vaccines of the future. How do they work? Over the last 30 years, we've learned an awful lot about how several different bacterial pathogens work. Pathogens like Salmonella and Listeria actually enter your cells and express their genes inside you (these are not viruses, mind you, but bacteria that go intracellular). We also know an awful lot about how to stop pathogenesis at certain steps. There are all kinds of mutants that are able to go intracellular, but are blocked at later stages of pathogenesis, so are unable to spread, or unable to express certain toxins, or otherwise unable to complete the disease process.

How does this help us build vaccines? These mutants that are blocked at later stages of pathogenesis actually elicit an immune response from the host. That is, when your body sees foreign bacteria in their cells, you are able to mount a potent immune response to it, so the second time you see Salmonella or Listeria, you are able to fight it off (though given that Salmonella has so many different varieties, it is quite difficult to vaccinate against all of them). It also allows you to mount both an antibody response and a cell-mediated response (these are two different immune responses that I will write about later). The long and the short of it is that most vaccines only elicit an antibody response, which doesn't protect well against pathogens that climb inside your cells to evade the antibodies.

Well, these days it is rather trivial to genetically engineer Salmonella. And Listeria is also able to be genetically engineered. So it's easy to put genes from another pathogen into them. (And before you cry, "What?! You're building a superbug?!! - it takes hundreds of genes working in concert to create a pathogen. One or two genes does not a pathogen make). One example of a live vector vaccine is here. Folks at the Center for Vaccine Development put part of the tetanus toxin into Salmonella. They then gave the Salmonella to mice, and found that the mice made antibodies to tetanus that have been previously shown to be able to protect them from infection.

So, big fat hairy deal. They've built a vaccine for an infection that there is already a potent vaccine available. Well, this is a potent demonstration that this technology is viable. There are a bunch of labs working to build vaccines against disease in a similar manner (including for diseases that don't currently have available vaccines).

What are the advantages of this approach? It's similar to the rice vaccine above:

1. You can get both cell-mediated and antibody immune responses, whereas most subunit vaccines that are available only give an antibody response. In non-science language: your immune system responds in a way that's more likely to prevent disease.

2. No needles! (You can just drink this).

3. Easier shipment and administering of the vaccine. And shipping to remote locations (think parts of Africa & Asia) is much simpler. That, and you don't need to have anyone who is highly trained giving the vaccine. Merely an eyedropper and a bottle to drop it into a glass of water will do.

4. Cheap. Growing Salmonella is easy. And building genetically modified Salmonella is infinitely easier than genetically modified plants or animals.

5. Generalizable. It is easy to imagine building multiple different vaccines in this manner, and then administering them simultaneously (either as a single organism, or a cocktail of several different bugs).

But what is the downside? The upfront costs will be high. New vaccines are expensive as the manpower to make them is highly skilled, and the number of tests that they have to undergo to demonstrate safety is high.

The other major downside is the PR side. The public at large is so woefully uneducated about basic science issues, and even conventional vaccines have been controversial in the public arena. I can only imagine the anti-vaccination folks now:

Genetically modified pathogens! *gasp* You're playing God!

Yep, every time you save a kid from a disease you're playing God. Some people think that's okay. I think that the time is right to start telling people about these vaccines so that when they do start to become commercially available that there isn't a visceral, knee-jerk reaction against them. When I tell people about what I do, they say, "You genetically engineer bacteria? Why would you want to do that?". If they're calm enough to sit down for a few minutes and talk to me about it, they often ultimately agree that it is a good idea.