I have begun to work with my friend George Georgiou on antibody development, and it’s really a kick. Basically, after having worked on functional RNAs for many years it’s sort of neat to be able to work with a biopolymer that actually has the ability to tightly bind ligands.
However, antibodies are more than just receptors. They represent our prime defenses against infection. And it has occurred to George and I and others that the new tools for dissecting sequence can now be used to dissect the immune response. Amazingly, you can immunize an animal with an antigen, wait a bit, and then sequence the mRNAs that encode immunoglubulins to determine what antibodies are the best (to a first approxiamtion). And because of our ability to synthesize genes de novo, we can go from immunization to sequencing to synthesis to build high affinity antibodies faster than if we were actually trying to clone the best antibody genes. Wild. I would never have believed that we could do this, a few years back. But now it seems poised to be the way in which many new antibodies will be made. More details on this method can be found in Reddy et al., Nature Biotechnology, 2010.
I think this tool will be especially useful in the biodefense realm, for a variety of reasons. One is that it is way easier to work with sequences from ‘hot’ immunizations than with the actual material. In this regard we have a great collaboration with Rob Davey at UTMB Galveston on identifying antibodies against proteins from Ebola.
Now, imagine that same scenario, but in a human, rather than an animal model. No, I don’t mean immunizing humans with Ebola. Sheesh. But what happens when we do have a zoonotic or bioterrorist event, and we don’t have the luxury of carrying out research against a completely novel pathogen. How do we fight it? We use our own immune responses. We sequence the repertoires of survivors (or even, as necessary, casualties) and determine what antibodies have come to the fore, make them, and use them as prophylactics and therapeutics against the disease. This is the ultimate ‘herd immunity,’ where we use our big brains and our fast machines to spread immunity throughout a population.
- originally posted on Sunday, September 19th, 2010